Steroid#Nomenclature

The steroid nucleus (core structure) is called gonane (cyclopentanoperhydrophenanthrene).{{cite journal | vauthors = Yang Y, Krin A, Cai X, Poopari MR, Zhang Y, Cheeseman JR, Xu Y | title = Conformations of Steroid Hormones: Infrared and Vibrational Circular Dichroism Spectroscopy | journal = Molecules | volume = 28 | issue = 2 | pages = 771 | date = January 2023 | pmid = 36677830 | pmc = 9864676 | doi = 10.3390/molecules28020771 | doi-access = free }} It is typically composed of seventeen carbon atoms, bonded in four fused rings: three six-member cyclohexane rings (rings A, B and C in the first illustration) and one five-member cyclopentane ring (the D ring). Steroids vary by the functional groups attached to this four-ring core and by the oxidation state of the rings. Sterols are forms of steroids with a hydroxy group at position three and a skeleton derived from cholestane.{{cite journal | journal = Pure Appl. Chem. | volume = 61 | issue = 10 | pages = 1783–1822 | year = 1989 | title = Nomenclature of steroids, recommendations 1989 | vauthors = Moss GP, ((the Working Party of the IUPAC-IUB Joint Commission on Biochemical Nomenclature)) | doi = 10.1351/pac198961101783 | s2cid = 97612891 | url = http://iupac.org/publications/pac/pdf/1989/pdf/6110x1783.pdf | access-date = 21 February 2012 | archive-date = 30 November 2012 | archive-url = https://web.archive.org/web/20121130182412/http://iupac.org/publications/pac/pdf/1989/pdf/6110x1783.pdf | url-status = live }} Also available with the same authors at {{cite journal | vauthors = | title = IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989 | journal = European Journal of Biochemistry | volume = 186 | issue = 3 | pages = 429–458 | date = December 1989 | pmid = 2606099 | doi = 10.1111/j.1432-1033.1989.tb15228.x | author-link3 = Josef Fried }}; Also available online at {{cite web|url= http://www.chem.qmul.ac.uk/iupac/steroid/3S01.html|title= The Nomenclature of Steroids|publisher= Queen Mary University of London|location= London, GBR|page= 3S-1.4|access-date= 10 May 2014|archive-date= 10 September 2017|archive-url= https://web.archive.org/web/20170910193822/http://www.chem.qmul.ac.uk/iupac/steroid/3S01.html|url-status= live}}{{rp|1785f}}Also available in print at {{cite book | vauthors = Hill RA, Makin HL, Kirk DN, Murphy GM | year= 1991 |title= Dictionary of Steroids |url= https://books.google.com/books?isbn=0-412-27060-9 |location= London, GBR |publisher= Chapman and Hall |pages= xxx–lix |isbn= 978-0-412-27060-4 |access-date= 20 June 2015}} Steroids can also be more radically modified, such as by changes to the ring structure, for example, cutting one of the rings. Cutting Ring B produces secosteroids one of which is vitamin D₃.

{{multiple image

| footer = 5α-dihydroprogesterone (5α-DHP), a steroid. The shape of the four rings of most steroids is illustrated (carbon atoms in black, oxygens in red and hydrogens in grey). The nonpolar "slab" of hydrocarbon in the middle (grey, black) and the polar groups at opposing ends (red) are common features of natural steroids. 5α-DHP is an endogenous steroid hormone and a biosynthetic intermediate.

| image1 = 5alpha-Dihydroprogesterone 3D spacefill.png

| alt1 = Filled-in diagram of a steroid

| caption1 = Space-filling representation

| image2 = 5alpha-Dihydroprogesterone 3D ball.png

| alt2 = Ball-and-stick diagram of the same steroid

| caption2 = Ball-and-stick representation

}}

{{See also|Gonane|Sterane}}

File:5alpha5betaSteroidIUPAC.png{{rp|1786f}}]]

Steroids are named after the steroid cholesterol{{cite web |vauthors=Harper D |title=sterol {{!}} Etymology, origin and meaning of sterol by etymonline |url=https://www.etymonline.com/word/sterol |access-date=19 March 2023 |website=Online Etymology Dictionary |archive-date=19 March 2023 |archive-url=https://web.archive.org/web/20230319092627/https://www.etymonline.com/word/sterol |url-status=live }} which was first described in gall stones from Ancient Greek chole- 'bile' and stereos 'solid'.{{cite journal |vauthors=Chevreul ME |author-link=Michel Eugène Chevreul |title=Recherches chimiques sur les corps gras, et particulièrement sur leurs combinaisons avec les alcalis. Sixième mémoire. Examen des graisses d'homme, de mouton, de boeuf, de jaguar et d'oie |trans-title=Chemical research on fatty substances, and particularly on their combinations with alkalis. Sixth memoir. Examination of human, sheep, beef, jaguar and goose fats |date=8 May 1815 |journal=Annales de Chimie et de Physique (Annals of Chemistry and Physics) |volume=2 |pages=339–372 |via=Deutsche Digitale Bibliothek |url=https://www.deutsche-digitale-bibliothek.de/item/254EFGXQPJNOVNAF575XO6K7MXD7EQOZ |access-date=11 September 2023 |language=fr |archive-date=4 October 2023 |archive-url=https://web.archive.org/web/20231004081946/https://www.deutsche-digitale-bibliothek.de/item/254EFGXQPJNOVNAF575XO6K7MXD7EQOZ |url-status=live }}{{cite book |url=https://books.google.com/books?id=DHCz1nhhYL8C&pg=PA346 |title=Annales de chimie et de physique (Annals of Chemistry and Physics) | vauthors = Arago F, Gay-Lussac JL |date=1816 |publisher=Chez Crochard |language=fr |page=346 |quote="Je nommerai cholesterine, de χολη, bile, et στερεος, solide, la substance cristallisée des calculs biliares humains, ... " (I will name cholesterine – from χολη (bile) and στερεος (solid) – the crystalized substance from human gallstones ... )}}{{cite web | url=https://www.acdlabs.com/iupac/nomenclature/93/r93_229.htm | title=R-2.4.1 Fusion nomenclature | access-date=22 November 2023 | archive-date=22 November 2023 | archive-url=https://web.archive.org/web/20231122015342/https://www.acdlabs.com/iupac/nomenclature/93/r93_229.htm | url-status=live }}

Gonane, also known as steran or cyclopentanoperhydrophenanthrene, the nucleus of all steroids and sterols,{{cite book|vauthors=Rogozkin VA|chapter=Anabolic Androgenic Steroids: Structure, Nomenclature, and Classification, Biological Properties|title=Metabolism of Anabolic-Androgenic Steroids|chapter-url=https://books.auho.com/books?id=hRsnmJRF1WgC&pg=PA1|date=14 June 1991|publisher=CRC Press|isbn=978-0-8493-6415-0|pages=1–|quote=The steroid structural base is a steran nucleus, a polycyclic C17 steran skeleton consisting of three condensed cyclohexane rings in nonlinear or phenanthrene junction (A, B, and C), and a cyclopentane ring (D).1,2}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite book| vauthors = Urich K | chapter = Sterols and Steroids |title=Comparative Animal Biochemistry| chapter-url = https://books.google.com/books?id=GLbcWyeaCGQC&pg=PA624 |date=16 September 1994|publisher=Springer Science & Business Media|isbn=978-3-540-57420-0|pages=624–}} is composed of seventeen carbon atoms in carbon-carbon bonds forming four fused rings in a three-dimensional shape. The three cyclohexane rings (A, B, and C in the first illustration) form the skeleton of a perhydro derivative of phenanthrene. The D ring has a cyclopentane structure. When the two methyl groups and eight carbon side chains (at C-17, as shown for cholesterol) are present, the steroid is said to have a cholestane framework. The two common 5α and 5β stereoisomeric forms of steroids exist because of differences in the side of the largely planar ring system where the hydrogen (H) atom at carbon-5 is attached, which results in a change in steroid A-ring conformation. Isomerisation at the C-21 side chain produces a parallel series of compounds, referred to as isosteroids.{{sfn|Greep|2013}}

Examples of steroid structures are:

In addition to the ring scissions (cleavages), expansions and contractions (cleavage and reclosing to a larger or smaller rings)—all variations in the carbon-carbon bond framework—steroids can also vary:

• in the bond orders within the rings,
• in the number of methyl groups attached to the ring (and, when present, on the prominent side chain at C17),
• in the functional groups attached to the rings and side chain, and
• in the configuration of groups attached to the rings and chain.{{rp|2–9}}

For instance, sterols such as cholesterol and lanosterol have a hydroxyl group attached at position C-3, while testosterone and progesterone have a carbonyl (oxo substituent) at C-3. Among these compounds, only lanosterol has two methyl groups at C-4. Cholesterol which has a C-5 to C-6 double bond, differs from testosterone and progesterone which have a C-4 to C-5 double bond.

Almost all biologically relevant steroids can be presented as a derivative of a parent cholesterol-like hydrocarbon structure that serves as a skeleton.{{cite journal |doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |date=3 April 2023 | vauthors = Masiutin MM, Yadav MK |journal=WikiJournal of Medicine |volume=10 |pages=29 |s2cid=257943362 |url=https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}{{cite journal|year=1989|title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989|journal=Eur J Biochem|volume=186|issue=3|pages=430|doi=10.1111/j.1432-1033.1989.tb15228.x|pmid=2606099|quote=3S‐1.0. Definition of steroids and sterols. Steroids are compounds possessing the skeleton of cyclopenta[a]phenanthrene or a skeleton derived therefrom by one or more bond scissions or ring expansions or contractions. Methyl groups are normally present at C-10 and C-13. An alkyl side chain may also be present at C-17. Sterols are steroids carrying a hydroxyl group at C-3 and most of the skeleton of cholestane.|quote-page=430}} These parent structures have specific names, such as pregnane, androstane, etc. The derivatives carry various functional groups called suffixes or prefixes after the respective numbers, indicating their position in the steroid nucleus. There are widely used trivial steroid names of natural origin with significant biologic activity, such as progesterone, testosterone or cortisol. Some of these names are defined in The Nomenclature of Steroids.{{cite journal | vauthors = | title = IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989, chapter 3S-4.9 | journal = European Journal of Biochemistry | volume = 186 | issue = 3 | pages = 429–458 | date = December 1989 | pmid = 2606099 | doi = 10.1111/j.1432-1033.1989.tb15228.x | url = https://iupac.qmul.ac.uk/steroid/3S04b.html#3S49 | quote = 3S‐4.9. Trivial names of important steroids Examples of trivial names retained for important steroid derivatives, these being mostly natural compounds of significant biological activity, are given in Table 2 | access-date = 19 February 2024 | archive-date = 19 February 2024 | archive-url = https://web.archive.org/web/20240219010052/https://iupac.qmul.ac.uk/steroid/3S04b.html#3S49 | url-status = live | url-access = subscription }} These trivial names can also be used as a base to derive new names, however, by adding prefixes only rather than suffixes, e.g., the steroid 17α-hydroxyprogesterone has a hydroxy group (-OH) at position 17 of the steroid nucleus comparing to progesterone.

The letters α and β{{cite journal | vauthors = | title = IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989, chapter 3S-1.4 | journal = European Journal of Biochemistry | volume = 186 | issue = 3 | pages = 429–458 | date = December 1989 | pmid = 2606099 | doi = 10.1111/j.1432-1033.1989.tb15228.x | quote = 3S‐1.4. Orientation of projection formulae. When the rings of a steroid are denoted as projections onto the plane of the paper, the formula is normally to be oriented as in 2a. An atom or group attached to a ring depicted as in the orientation 2a is termed α (alpha) if it lies below the plane of the paper or β (beta) if it lies above the plane of the paper. | quote-page = 431 }} denote absolute stereochemistry at chiral centers—a specific nomenclature distinct from the R/S convention{{cite book| vauthors = Favre HA, Powell WH |title=Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013|publisher=The Royal Society of Chemistry|year=2014|isbn=978-0-85404-182-4|doi=10.1039/9781849733069|chapter=P-91|quote-page=868|quote=P‐91.2.1.1 Cahn-Ingold-Prelog (CIP) stereodescriptors. Some stereodescriptors described in the Cahn-Ingold-Prelog (CIP) priority system, called ‘CIP stereodescriptors’, are recommended to specify the configuration of organic compounds, as described and exemplified in this Chapter and applied in Chapters P‐1 through P‐8, and in the nomenclature of natural products in Chapter P-10. The following stereodescriptors are used as preferred stereodescriptors (see P‐92.1.2): (a) ‘R’ and ‘S’, to designate the absolute configuration of tetracoordinate (quadriligant) chirality centers;}} of organic chemistry to denote absolute configuration of functional groups, known as Cahn–Ingold–Prelog priority rules. The R/S convention assigns priorities to substituents on a chiral center based on their atomic number. The highest priority group is assigned to the atom with the highest atomic number, and the lowest priority group is assigned to the atom with the lowest atomic number. The molecule is then oriented so that the lowest priority group points away from the viewer, and the remaining three groups are arranged in order of decreasing priority around the chiral center. If this arrangement is clockwise, it is assigned an R configuration; if it is counterclockwise, it is assigned an S configuration.{{cite web | url=https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_v2.0_%28Soderberg%29/03%3A_Conformations_and_Stereochemistry/3.05%3A_Naming_chiral_centers-_the_R_and_S_system | title=3.5: Naming chiral centers- the R and S system | date=11 August 2018 | access-date=16 October 2023 | archive-date=1 November 2023 | archive-url=https://web.archive.org/web/20231101155825/https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book:_Organic_Chemistry_with_a_Biological_Emphasis_v2.0_(Soderberg)/03:_Conformations_and_Stereochemistry/3.05:_Naming_chiral_centers-_the_R_and_S_system | url-status=live }} In contrast, steroid nomenclature uses α and β to denote stereochemistry at chiral centers. The α and β designations are based on the orientation of substituents relative to each other in a specific ring system. In general, α refers to a substituent that is oriented towards the plane of the ring system, while β refers to a substituent that is oriented away from the plane of the ring system. In steroids drawn from the standard perspective used in this paper, α-bonds are depicted on figures as dashed wedges and β-bonds as solid wedges.

The name "11-deoxycortisol" is an example of a derived name that uses cortisol as a parent structure without an oxygen atom (hence "deoxy") attached to position 11 (as a part of a hydroxy group).{{cite book| vauthors = Favre HA, Powell WH |title=Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013|publisher=The Royal Society of Chemistry|year=2014|isbn=978-0-85404-182-4|doi=10.1039/9781849733069|chapter=P-13.8.1.1|quote-page=66|quote=P‐13.8.1.1 The prefix ‘de’ (not ‘des’), followed by the name of a group or atom (other than hydrogen), denotes removal (or loss) of that group and addition of the necessary hydrogen atoms, i.e., exchange of that group with hydrogen atoms. As an exception, ‘deoxy’, when applied to hydroxy compounds, denotes the removal of an oxygen atom from an –OH group with the reconnection of the hydrogen atom. ‘Deoxy’ is extensively used as a subtractive prefix in carbohydrate nomenclature (see P‐102.5.3).}} The numbering of positions of carbon atoms in the steroid nucleus is set in a template found in the Nomenclature of Steroids{{cite journal|year=1989|title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989|journal=Eur J Biochem|volume=186|issue=3|pages=430|doi=10.1111/j.1432-1033.1989.tb15228.x|pmid=2606099|quote=3S-1.1. Numbering and ring letters. Steroids are numbered and rings are lettered as in formula 1|quote-page=430}} that is used regardless of whether an atom is present in the steroid in question.

Unsaturated carbons (generally, ones that are part of a double bond) in the steroid nucleus are indicated by changing -ane to -ene.{{cite journal |title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989 |journal=Eur J Biochem |date=1989 |volume=186 |issue=3 |pages=436–437 |doi=10.1111/j.1432-1033.1989.tb15228.x |pmid=2606099 |quote-page=436-437|quote=3S‐2.5 Unsaturation. Unsaturation is indicated by changing -ane to -ene, -adiene, -yne etc., or -an- to -en-, -adien-, -yn- etc. Examples: Androst-5-ene, not 5-androstene; 5α-Cholest-6-ene; 5β-Cholesta-7,9(11)-diene; 5α-Cholest-6-en-3β-ol. Notes. 1) It is now recommended that the locant of a double bond is always adjacent to the syllable designating the unsaturation.[...] 3) The use of Δ (Greek capital delta) character is not recommended to designate unsaturation in individual names. It may be used, however, in generic terms, like ‘Δ⁵-steroids’}} This change was traditionally done in the parent name, adding a prefix to denote the position, with or without Δ (Greek capital delta) which designates unsaturation, for example, 4-pregnene-11β,17α-diol-3,20-dione (also Δ⁴-pregnene-11β,17α-diol-3,20-dione) or 4-androstene-3,11,17-trione (also Δ⁴-androstene-3,11,17-trione). However, the Nomenclature of Steroids recommends the locant of a double bond to be always adjacent to the syllable designating the unsaturation, therefore, having it as a suffix rather than a prefix, and without the use of the Δ character, i.e. pregn-4-ene-11β,17α-diol-3,20-dione or androst-4-ene-3,11,17-trione. The double bond is designated by the lower-numbered carbon atom, i.e. "Δ⁴-" or "4-ene" means the double bond between positions 4 and 5. The saturation of carbons of a parent steroid can be done by adding "dihydro-" prefix,{{cite book| vauthors = Favre HA, Powell WH |title=Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013|publisher=The Royal Society of Chemistry|year=2014|isbn=978-0-85404-182-4|doi=10.1039/9781849733069|chapter=P-3|quote=P-31.2.2 General methodology. ‘Hydro’ and ‘dehydro’ prefixes are associated with hydrogenation and dehydrogenation, respectively, of a double bond; thus, multiplying prefixes of even values, as ‘di’, ‘tetra’, etc. are used to indicate the saturation of double bond(s), for example ‘dihydro’, ‘tetrahydro’; or creation of double (or triple) bonds, as ‘didehydro’, etc. In names, they are placed immediately at the front of the name of the parent hydride and in front of any nondetachable prefixes. Indicated hydrogen atoms have priority over ‘hydro‘ prefixes for low locants. If indicated hydrogen atoms are present in a name, the ‘hydro‘ prefixes precede them.}} i.e., a saturation of carbons 4 and 5 of testosterone with two hydrogen atoms is 4,5α-dihydrotestosterone or 4,5β-dihydrotestosterone. Generally, when there is no ambiguity, one number of a hydrogen position from a steroid with a saturated bond may be omitted, leaving only the position of the second hydrogen atom, e.g., 5α-dihydrotestosterone or 5β-dihydrotestosterone. The Δ⁵-steroids are those with a double bond between carbons 5 and 6 and the Δ⁴ steroids are those with a double bond between carbons 4 and 5.{{cite journal |vauthors=Miller WL, Auchus RJ |title=The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders |journal=Endocr Rev |volume=32 |issue=1 |pages=81–151 |date=February 2011 |pmid=21051590 |pmc=3365799 |doi=10.1210/er.2010-0013}}

The abbreviations like "P4" for progesterone and "A4" for androstenedione for refer to Δ⁴-steroids, while "P5" for pregnenolone and "A5" for androstenediol refer to Δ⁵-steroids.

The suffix -ol denotes a hydroxy group, while the suffix -one denotes an oxo group. When two or three identical groups are attached to the base structure at different positions, the suffix is indicated as -diol or -triol for hydroxy, and -dione or -trione for oxo groups, respectively. For example, 5α-pregnane-3α,17α-diol-20-one has a hydrogen atom at the 5α position (hence the "5α-" prefix), two hydroxy groups (-OH) at the 3α and 17α positions (hence "3α,17α-diol" suffix) and an oxo group (=O) at the position 20 (hence the "20-one" suffix). However, erroneous use of suffixes can be found, e.g., "5α-pregnan-17α-diol-3,11,20-trione"{{cite web| url=https://scholar.google.com/scholar?&q=%225%CE%B1-pregnan-17%CE%B1-diol-3%2C11%2C20-trione%22| title=Google Scholar search results for "5α-pregnan-17α-diol-3,11,20-trione" that is an incorrect name| year=2022| access-date=1 October 2023| archive-date=6 October 2023| archive-url=https://web.archive.org/web/20231006203706/https://scholar.google.com/scholar?&q=%225%CE%B1-pregnan-17%CE%B1-diol-3%2C11%2C20-trione%22| url-status=live}} [sic] — since it has just one hydroxy group (at 17α) rather than two, then the suffix should be -ol, rather than -diol, so that the correct name to be "5α-pregnan-17α-ol-3,11,20-trione".

According to the rule set in the Nomenclature of Steroids, the terminal "e" in the parent structure name should be elided before the vowel (the presence or absence of a number does not affect such elision).{{cite journal |title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989 |journal=Eur J Biochem |date=1989 |volume=186 |issue=3 |pages=429–458 |doi=10.1111/j.1432-1033.1989.tb15228.x |pmid=2606099|quote-page=441|quote=3S-4. FUNCTIONAL GROUPS. 3S-4.0. General. Nearly all biologically important steroids are derivatives of the parent hydrocarbons (cf. Table 1) carrying various functional groups. [...] Suffixes are added to the name of the saturated or unsaturated parent system (see 33-2.5), the terminal e of -ane, -ene, -yne, -adiene etc. being elided before a vowel (presence or absence of numerals has no effect on such elisions).}} This means, for instance, that if the suffix immediately appended to the parent structure name begins with a vowel, the trailing "e" is removed from that name. An example of such removal is "5α-pregnan-17α-ol-3,20-dione", where the last "e" of "pregnane" is dropped due to the vowel ("o") at the beginning of the suffix -ol. Some authors incorrectly use this rule, eliding the terminal "e" where it should be kept, or vice versa.{{cite web| url=https://scholar.google.com/scholar?q=%225%CE%B1-pregnane-17%CE%B1-ol-3%2C20-dione%22| title=Google Scholar search results for "5α-pregnane-17α-ol-3,20-dione" that is an incorrect name| year=2022| access-date=1 October 2023| archive-date=7 October 2023| archive-url=https://web.archive.org/web/20231007002325/https://scholar.google.com/scholar?q=%225%CE%B1-pregnane-17%CE%B1-ol-3%2C20-dione%22| url-status=live}}

The term "11-oxygenated" refers to the presence of an oxygen atom as an oxo (=O) or hydroxy (-OH) substituent at carbon 11. "Oxygenated" is consistently used within the chemistry of the steroids{{cite journal| vauthors = Makin HL, Trafford DJ |year=1972|title=The chemistry of the steroids|journal=Clinics in Endocrinology and Metabolism|volume=1|issue=2|pages=333–360|doi=10.1016/S0300-595X(72)80024-0}} since the 1950s.{{cite journal | vauthors = Bongiovanni AM, Clayton GW | title = Simplified method for estimation of 11-oxygenated neutral 17-ketosteroids in urine of individuals with adrenocortical hyperplasia | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 85 | issue = 3 | pages = 428–429 | date = March 1954 | pmid = 13167092 | doi = 10.3181/00379727-85-20905 | s2cid = 8408420 }} Some studies use the term "11-oxyandrogens"{{cite journal| vauthors = Slaunwhite Jr WR, Neely L, Sandberg AA |year=1964|title=The metabolism of 11-Oxyandrogens in human subjects|journal=Steroids|volume=3|issue=4|pages=391–416|doi=10.1016/0039-128X(64)90003-0}}{{cite journal | vauthors = Taylor AE, Ware MA, Breslow E, Pyle L, Severn C, Nadeau KJ, Chan CL, Kelsey MM, Cree-Green M | display-authors = 6 | title = 11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome | journal = Journal of the Endocrine Society | volume = 6 | issue = 7 | pages = bvac037 | date = July 2022 | pmid = 35611324 | pmc = 9123281 | doi = 10.1210/jendso/bvac037 | doi-access = free }} as an abbreviation for 11-oxygenated androgens, to emphasize that they all have an oxygen atom attached to carbon at position 11.{{cite journal | vauthors = Turcu AF, Rege J, Auchus RJ, Rainey WE | title = 11-Oxygenated androgens in health and disease | journal = Nature Reviews. Endocrinology | volume = 16 | issue = 5 | pages = 284–296 | date = May 2020 | pmid = 32203405 | pmc = 7881526 | doi = 10.1038/s41574-020-0336-x }}{{cite journal | vauthors = Barnard L, du Toit T, Swart AC | title = Back where it belongs: 11β-hydroxyandrostenedione compels the re-assessment of C11-oxy androgens in steroidogenesis | journal = Molecular and Cellular Endocrinology | volume = 525 | pages = 111189 | date = April 2021 | pmid = 33539964 | doi = 10.1016/j.mce.2021.111189 | s2cid = 231776716 }} However, in chemical nomenclature, the prefix "oxy" is associated with ether functional groups, i.e., a compound with an oxygen atom connected to two alkyl or aryl groups (R-O-R),{{cite book| vauthors = Favre H, Powell W |title=Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013|publisher=The Royal Society of Chemistry|year=2014|isbn=978-0-85404-182-4|doi=10.1039/9781849733069|chapter=Appendix 2|quote-page=1112|quote=oxy* –O– P-15.3.1.2.1.1; P-63.2.2.1.1}} therefore, using "oxy" within the name of a steroid class may be misleading. One can find clear examples of "oxygenated" to refer to a broad class of organic molecules containing a variety of oxygen containing functional groups in other domains of organic chemistry,{{cite journal| vauthors = Barrientos EJ, Lapuerta M, Boehman AL |date=August 2013|title=Group additivity in soot formation for the example of C-5 oxygenated hydrocarbon fuels |journal=Combustion and Flame|language=en|volume=160|issue=8|pages=1484–1498|doi=10.1016/j.combustflame.2013.02.024|bibcode=2013CoFl..160.1484B }} and it is appropriate to use this convention.

Even though "keto" is a standard prefix in organic chemistry, the 1989 recommendations of the Joint Commission on Biochemical Nomenclature discourage the application of the prefix "keto" for steroid names, and favor the prefix "oxo" (e.g., 11-oxo steroids rather than 11-keto steroids), because "keto" includes the carbon that is part of the steroid nucleus and the same carbon atom should not be specified twice.{{cite journal|year=1989|title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989|journal=Eur J Biochem|volume=186|issue=3|pages=429–58|doi=10.1111/j.1432-1033.1989.tb15228.x|pmid=2606099|quote=The prefix oxo- should also be used in connection with generic terms, e.g., 17-oxo steroids. The term ‘17-keto steroids’, often used in the medical literature, is incorrect because C-17 is specified twice, as the term keto denotes C=O|quote-page=430}}

Steroids are present across all domains of life, including bacteria, archaea, and eukaryotes. In eukaryotes, steroids are particularly abundant in fungi, plants, and animals.{{cite encyclopedia|url=https://www.britannica.com/science/steroid/Biological-significance-of-steroids|title=Biological significance of steroids|access-date=12 February 2024|archive-date=12 February 2024|archive-url=https://web.archive.org/web/20240212190424/https://www.britannica.com/science/steroid/Biological-significance-of-steroids|url-status=live}}{{cite news | url=https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_%28Boundless%29/17%3A_Industrial_Microbiology/17.02%3A_Microbial_Products_in_the_Health_Industry/17.2C%3A_Steroids | title=17.2C: Steroids | newspaper=Biology Libretexts | date=3 July 2018 | access-date=12 February 2024 | archive-date=12 February 2024 | archive-url=https://web.archive.org/web/20240212190425/https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/17:_Industrial_Microbiology/17.02:_Microbial_Products_in_the_Health_Industry/17.2C:_Steroids | url-status=live }}

Eukaryotic cells, encompassing animals, plants, fungi, and protists, are characterized by their complex cellular structures, including a true nucleus and membrane-bound organelles.{{Cite journal |title=Steroids distribution |date=2021 |doi=10.1073/pnas.2101276118 |pmid=34131078 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=118 |issue=25 |pmc=8237579 | vauthors = Hoshino Y, Gaucher EA |doi-access=free }} Sterols, a subgroup of steroids, play crucial roles in maintaining membrane fluidity, supporting cell signaling, and enhancing stress tolerance. These compounds are integral to eukaryotic membranes, where they contribute to membrane integrity and functionality.{{Cite web |title=Steroids distribution |url=https://www.drugs.com/monograph/calcium-salts.html |access-date=17 May 2024 |archive-date=18 January 2017 |archive-url=https://web.archive.org/web/20170118041341/https://www.drugs.com/monograph/calcium-salts.html |url-status=bot: unknown }}

During eukaryogenesis—the evolutionary process that gave rise to modern eukaryotic cells—steroids likely facilitated the endosymbiotic acquisition of mitochondria.{{Cite journal |title=Species distribution |date=2021 |doi=10.1073/pnas.2101276118 |pmid=34131078 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=118 |issue=25 |pmc=8237579 | vauthors = Hoshino Y, Gaucher EA |doi-access=free }}

Although sterol biosynthesis is rare in prokaryotes, certain bacteria, including Methylococcus capsulatus, specific methanotrophs, myxobacteria, and the planctomycete Gemmata obscuriglobus, are capable of producing sterols. In G. obscuriglobus, sterols are essential for cell viability, but their roles in other bacteria remain poorly understood.{{cite book | vauthors = Franke JD | chapter = Sterol Biosynthetic Pathways and Their Function in Bacteria. | veditors = Villa TG, de Miguel Bouzas T | title = Developmental Biology in Prokaryotes and Lower Eukaryotes | date = 2021 | pages = 215-227 | doi = 10.1007/978-3-030-77595-7_9 | isbn = 978-3-030-77595-7 | location = Cham | publisher = Springer}}

Prokaryotic sterol synthesis involves the tetracyclic steroid framework, as found in myxobacteria,{{cite journal | vauthors = Bode HB, Zeggel B, Silakowski B, Wenzel SC, Reichenbach H, Müller R | title = Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca | journal = Molecular Microbiology | volume = 47 | issue = 2 | pages = 471–81 | date = Jan 2003 | pmid = 12519197 | doi = 10.1046/j.1365-2958.2003.03309.x | s2cid = 37959511 | doi-access = }} as well as hopanoids, pentacyclic lipids that regulate bacterial membrane functions.{{cite journal | vauthors = Siedenburg G, Jendrossek D | title = Squalene-hopene cyclases | journal = Applied and Environmental Microbiology | volume = 77 | issue = 12 | pages = 3905–15 | date = Jun 2011 | pmid = 21531832 | pmc = 3131620 | doi = 10.1128/AEM.00300-11 | bibcode = 2011ApEnM..77.3905S }} These sterol biosynthetic pathways may have originated in bacteria or been transferred from eukaryotes.{{cite journal | vauthors = Desmond E, Gribaldo S | title = Phylogenomics of sterol synthesis: insights into the origin, evolution, and diversity of a key eukaryotic feature | journal = Genome Biology and Evolution | volume = 1 | pages = 364–81 | year = 2009 | pmid = 20333205 | pmc = 2817430 | doi = 10.1093/gbe/evp036 }}

Sterol synthesis depends on two key enzymes: squalene monooxygenase and oxidosqualene cyclase. Phylogenetic analyses of oxidosqualene cyclase (Osc) suggest that some bacterial Osc genes may have been acquired via horizontal gene transfer from eukaryotes, as certain bacterial Osc proteins closely resemble their eukaryotic homologs.

Fungal steroids include the ergosterols, which are involved in maintaining the integrity of the fungal cellular membrane. Various antifungal drugs, such as amphotericin B and azole antifungals, utilize this information to kill pathogenic fungi.{{cite book | vauthors = Bhetariya PJ, Sharma N, Singh P, Tripathi P, Upadhyay SK, Gautam P | veditors = Arora C, Sajid A, Kalia V | title=Drug Resistance in Bacteria, Fungi, Malaria, and Cancer|publisher=Springer|isbn=978-3-319-48683-3|language=en|chapter=Human Fungal Pathogens and Drug Resistance Against Azole Drugs| date = 21 March 2017}} Fungi can alter their ergosterol content (e.g. through loss of function mutations in the enzymes ERG3 or ERG6, inducing depletion of ergosterol, or mutations that decrease the ergosterol content) to develop resistance to drugs that target ergosterol.

Ergosterol is analogous to the cholesterol found in the cellular membranes of animals (including humans), or the phytosterols found in the cellular membranes of plants.{{cite book| veditors = Kavanagh K |title=Fungi: Biology and Applications|date=8 September 2017|publisher=John Wiley & Sons, Inc.|isbn=978-1-119-37431-2|language=en}} All mushrooms contain large quantities of ergosterol, in the range of tens to hundreds of milligrams per 100 grams of dry weight. Oxygen is necessary for the synthesis of ergosterol in fungi.

Ergosterol is responsible for the vitamin D content found in mushrooms; ergosterol is chemically converted into provitamin D2 by exposure to ultraviolet light. Provitamin D2 spontaneously forms vitamin D2. However, not all fungi utilize ergosterol in their cellular membranes; for example, the pathogenic fungal species Pneumocystis jirovecii does not, which has important clinical implications (given the mechanism of action of many antifungal drugs). Using the fungus Saccharomyces cerevisiae as an example, other major steroids include ergosta‐5,7,22,24(28)‐tetraen‐3β‐ol, zymosterol, and lanosterol. S. cerevisiae utilizes 5,6‐dihydroergosterol in place of ergosterol in its cell membrane.

Plant steroids include steroidal alkaloids found in Solanaceae{{cite journal | vauthors = Wink M | title = Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective | journal = Phytochemistry | volume = 64 | issue = 1 | pages = 3–19 | date = Sep 2003 | pmid = 12946402 | doi = 10.1016/S0031-9422(03)00300-5 | bibcode = 2003PChem..64....3W }} and Melanthiaceae (specially the genus Veratrum),{{cite book | vauthors = Wink M, Van Wyk BE |title=Mind-altering and poisonous plants of the world |date=2008 |publisher=Timber press inc. |location=Portland (Oregon USA) and Salusbury (London England) |isbn=978-0-88192-952-2 |pages=252, 253 and 254}} cardiac glycosides,{{cite book | vauthors = Wink M, van Wyk BE |title=Mind-altering and poisonous plants of the world |date=2008 |publisher=Timber press inc. |location=Portland (Oregon USA) and Salusbury (London England) |isbn=978-0-88192-952-2 |pages=324, 325 and 326}} the phytosterols and the brassinosteroids (which include several plant hormones).

Animal steroids include compounds of vertebrate and insect origin, the latter including ecdysteroids such as ecdysterone (controlling molting in some species). Vertebrate examples include the steroid hormones and cholesterol; the latter is a structural component of cell membranes that helps determine the fluidity of cell membranes and is a principal constituent of plaque (implicated in atherosclerosis). Steroid hormones include:

• Sex hormones, which influence sex differences and support puberty and reproduction. These include androgens, estrogens, and progestogens.
• Corticosteroids, including most synthetic steroid drugs, with natural product classes the glucocorticoids (which regulate many aspects of metabolism and immune function) and the mineralocorticoids (which help maintain blood volume and control renal excretion of electrolytes)
• Anabolic steroids, natural and synthetic, which interact with androgen receptors to increase muscle and bone synthesis. In popular use, the term "steroids" often refers to anabolic steroids.

{{expand section|A more detailed explanation of function would also be beneficial|date=January 2019|small=yes}}

The major classes of steroid hormones, with prominent members and examples of related functions, are:{{cite journal |vauthors=Ericson-Neilsen W, Kaye AD |title=Steroids: pharmacology, complications, and practice delivery issues |journal=Ochsner J |volume=14 |issue=2 |pages=203–7 |date=2014 |pmid=24940130 |pmc=4052587}}{{cite web | url=https://www.mdpi.com/journal/ijms/special_issues/steroid_hormones_sex | title=International Journal of Molecular Sciences | access-date=12 February 2024 | archive-date=12 February 2024 | archive-url=https://web.archive.org/web/20240212192445/https://www.mdpi.com/journal/ijms/special_issues/steroid_hormones_sex | url-status=live }}

• Corticosteroids:
• Glucocorticoids:
• Cortisol, a glucocorticoid whose functions include stress response and immunosuppression
• Mineralocorticoids:
• Aldosterone, a mineralocorticoid that helps regulate blood pressure through water and electrolyte balance in the kidneys
• Sex steroids:
• Progestogens:
• Progesterone, which regulates cyclical changes in the endometrium of the uterus and maintains a pregnancy
• Androgens:
• Testosterone, which contributes to the development and maintenance of male secondary sex characteristics
• Estrogens:
• Estradiol, which contributes to the development and maintenance of female secondary sex characteristics

Additional classes of steroids include:

• Neurosteroids such as {{abbrlink|DHEA|dehydroepiandrosterone}} and allopregnanolone
• Bile acids such as taurocholic acid
• Aminosteroid neuromuscular blocking agents (mainly synthetic) such as pancuronium bromide
• Steroidal antiandrogens (mainly synthetic) such as cyproterone acetate
• Steroidogenesis inhibitors (mainly exogenous) such as alfatradiol
• Membrane sterols such as cholesterol, ergosterol, and various phytosterols
• Toxins such as steroidal saponins and cardenolides/cardiac glycosides

As well as the following class of secosteroids (open-ring steroids):

• Vitamin D forms such as ergocalciferol, cholecalciferol, and calcitriol

Steroids can be classified based on their chemical composition.{{cite book|title=Steroids (Health and Medical Issues Today)| vauthors = Zorea A |publisher=Greenwood Press|year=2014|isbn=978-1-4408-0299-7|location=Westport, CT|pages=10–12}} One example of how MeSH performs this classification is available at the Wikipedia MeSH catalog. Examples of this classification include:

Image:Cholecalciferol.svg (vitamin D{{ssub|3}}), an example of a 9,10-secosteroid]]

Image:Cyclopamine.svg, an example of a complex C-nor-D-homosteroid]]

In biology, it is common to name the above steroid classes by the number of carbon atoms present when referring to hormones: C₁₈-steroids for the estranes (mostly estrogens), C₁₉-steroids for the androstanes (mostly androgens), and C₂₁-steroids for the pregnanes (mostly corticosteroids).{{cite web |title=C19-steroid hormone biosynthetic pathway – Ontology Browser – Rat Genome Database |url=https://rgd.mcw.edu/rgdweb/ontology/view.html?acc_id=PW:0000770 |website=rgd.mcw.edu |access-date=11 April 2022 |archive-date=12 May 2023 |archive-url=https://web.archive.org/web/20230512220253/https://rgd.mcw.edu/rgdweb/ontology/view.html?acc_id=PW:0000770 |url-status=live }} The classification "17-ketosteroid" is also important in medicine.

The gonane (steroid nucleus) is the parent 17-carbon tetracyclic hydrocarbon molecule with no alkyl sidechains.{{cite journal | vauthors = Edgren RA, Stanczyk FZ | title = Nomenclature of the gonane progestins | journal = Contraception | volume = 60 | issue = 6 | pages = 313 | date = Dec 1999 | pmid = 10715364 | doi = 10.1016/S0010-7824(99)00101-8 }}

Secosteroids (Latin seco, "to cut") are a subclass of steroidal compounds resulting, biosynthetically or conceptually, from scission (cleavage) of parent steroid rings (generally one of the four). Major secosteroid subclasses are defined by the steroid carbon atoms where this scission has taken place. For instance, the prototypical secosteroid cholecalciferol, vitamin D₃ (shown), is in the 9,10-secosteroid subclass and derives from the cleavage of carbon atoms C-9 and C-10 of the steroid B-ring; 5,6-secosteroids and 13,14-steroids are similar.{{cite journal | vauthors = Hanson JR | title = Steroids: partial synthesis in medicinal chemistry | journal = Natural Product Reports | volume = 27 | issue = 6 | pages = 887–99 | date = Jun 2010 | pmid = 20424788 | doi = 10.1039/c001262a }}

Norsteroids (nor-, L. norma; "normal" in chemistry, indicating carbon removal){{cite web | publisher = International Union of Pure and Applied Chemistry (IUPAC) | year = 1999 | title = IUPAC Recommendations: Skeletal Modification in Revised Section F: Natural Products and Related Compounds (IUPAC Recommendations 1999) | url = http://www.chem.qmul.ac.uk/iupac/sectionF/RF41.html#41 | access-date = 20 May 2014 | archive-date = 4 March 2016 | archive-url = https://web.archive.org/web/20160304041709/http://www.chem.qmul.ac.uk/iupac/sectionF/RF41.html#41 | url-status = live }} and homosteroids (homo-, Greek homos; "same", indicating carbon addition) are structural subclasses of steroids formed from biosynthetic steps. The former involves enzymic ring expansion-contraction reactions, and the latter is accomplished (biomimetically) or (more frequently) through ring closures of acyclic precursors with more (or fewer) ring atoms than the parent steroid framework.{{cite journal | vauthors = Wolfing J | date = 2007 | title = Recent developments in the isolation and synthesis of D-homosteroids and related compounds | journal = Arkivoc | volume = 2007 | issue = 5 | pages = 210–230 | doi = 10.3998/ark.5550190.0008.517 | url = http://www.arkat-usa.org/get-file/19924/ | doi-access = free | hdl = 2027/spo.5550190.0008.517 | hdl-access = free | access-date = 20 May 2014 | archive-date = 1 February 2013 | archive-url = https://web.archive.org/web/20130201091834/http://www.arkat-usa.org/get-file/19924/ | url-status = live }}

Combinations of these ring alterations are known in nature. For instance, ewes who graze on corn lily ingest cyclopamine (shown) and veratramine, two of a sub-family of steroids where the C- and D-rings are contracted and expanded respectively via a biosynthetic migration of the original C-13 atom. Ingestion of these C-nor-D-homosteroids results in birth defects in lambs: cyclopia from cyclopamine and leg deformity from veratramine.{{cite book | veditors = Corey EJ, Li JJ | title = Total synthesis of natural products: at the frontiers of organic chemistry | vauthors = Gao G, Chen C | chapter = Nakiterpiosin | chapter-url = https://books.google.com/books?id=UT5EAAAAQBAJ | doi = 10.1007/978-3-642-34065-9 | date = 2012 | publisher = Springer | location = Berlin | isbn = 978-3-642-34064-2 | s2cid = 92690863 }} A further C-nor-D-homosteroid (nakiterpiosin) is excreted by Okinawan cyanobacteriosponges. e.g., Terpios hoshinota, leading to coral mortality from black coral disease.{{cite journal | vauthors = Uemura E, Kita M, Arimoto H, Kitamura M | date = 2009 | title = Recent aspects of chemical ecology: Natural toxins, coral communities, and symbiotic relationships | journal = Pure Appl. Chem. | volume = 81 | issue = 6 | pages = 1093–1111 | doi = 10.1351/PAC-CON-08-08-12| doi-access = free }} Nakiterpiosin-type steroids are active against the signaling pathway involving the smoothened and hedgehog proteins, a pathway which is hyperactive in a number of cancers.{{citation needed|date=March 2019}}

Steroids and their metabolites often function as signalling molecules (the most notable examples are steroid hormones), and steroids and phospholipids are components of cell membranes.{{cite book|title=Human physiology : an integrated approach| vauthors = Silverthorn DU, Johnson BR, Ober WC, Ober CE, Silverthorn AC |isbn=978-0-321-98122-6|edition= Seventh|location=[San Francisco] | publisher = Sinauer Associates; W.H. Freeman & Co. |oclc=890107246|year = 2016}} Steroids such as cholesterol decrease membrane fluidity.{{cite book |vauthors=Sadava D, Hillis DM, Heller HC, Berenbaum MR | title = Life: The Science of Biology | edition = 9 | publisher = Freeman | location = San Francisco | year = 2011 | pages = 105–114 | isbn = 978-1-4292-4646-0 }}

Similar to lipids, steroids are highly concentrated energy stores. However, they are not typically sources of energy; in mammals, they are normally metabolized and excreted.

Steroids play critical roles in a number of disorders, including malignancies like prostate cancer, where steroid production inside and outside the tumour promotes cancer cell aggressiveness.{{cite journal|pmid=27672740| title = Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment| year = 2016 | doi=10.1002/ijc.30450| journal=Int. J. Cancer| volume = 140| issue = 2| pages = 358–369| vauthors=Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R| s2cid = 2354209| doi-access = free}}

File:Sterol synthesis.svg (PP or IPP) and dimethylallyl pyrophosphate (DMAPP) form geranyl pyrophosphate (GPP), squalene and lanosterol (which can be converted into other steroids).]]

The hundreds of steroids found in animals, fungi, and plants are made from lanosterol (in animals and fungi; see examples above) or cycloartenol (in other eukaryotes). Both lanosterol and cycloartenol derive from cyclization of the triterpenoid squalene. Lanosterol and cycloartenol are sometimes called protosterols because they serve as the starting compounds for all other steroids.

Steroid biosynthesis is an anabolic pathway which produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals (compared to many other organisms), making the pathway a common target for antibiotics and other anti-infection drugs. Steroid metabolism in humans is also the target of cholesterol-lowering drugs, such as statins. In humans and other animals the biosynthesis of steroids follows the mevalonate pathway, which uses acetyl-CoA as building blocks for dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP).{{cite journal | vauthors = Grochowski LL, Xu H, White RH | title = Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis of isopentenyl diphosphate | journal = Journal of Bacteriology | volume = 188 | issue = 9 | pages = 3192–8 | date = May 2006 | pmid = 16621811 | pmc = 1447442 | doi = 10.1128/JB.188.9.3192-3198.2006 }}{{better source needed|date=July 2014}}

In subsequent steps DMAPP and IPP conjugate to form farnesyl diphosphate (FPP), which further conjugates with each other to form the linear triterpenoid squalene. Squalene biosynthesis is catalyzed by squalene synthase, which belongs to the squalene/phytoene synthase family. Subsequent epoxidation and cyclization of squalene generate lanosterol, which is the starting point for additional modifications into other steroids (steroidogenesis).{{cite journal| vauthors = Chatuphonprasert W, Jarukamjorn K, Ellinger I |date=12 September 2018|title=Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta|journal=Frontiers in Pharmacology|volume=9|pages=1027|doi=10.3389/fphar.2018.01027|issn=1663-9812|pmc=6144938|pmid=30258364|doi-access=free}} In other eukaryotes, the cyclization product of epoxidized squalene (oxidosqualene) is cycloartenol.

File:Mevalonate pathway.svg

{{Main|Mevalonate pathway}}

The mevalonate pathway (also called HMG-CoA reductase pathway) begins with acetyl-CoA and ends with dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP).

DMAPP and IPP donate isoprene units, which are assembled and modified to form terpenes and isoprenoids{{cite journal | vauthors = Kuzuyama T, Seto H | title = Diversity of the biosynthesis of the isoprene units | journal = Natural Product Reports | volume = 20 | issue = 2 | pages = 171–83 | date = Apr 2003 | pmid = 12735695 | doi = 10.1039/b109860h }} (a large class of lipids, which include the carotenoids and form the largest class of plant natural products).{{cite journal | vauthors = Dubey VS, Bhalla R, Luthra R | title = An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants | journal = Journal of Biosciences | volume = 28 | issue = 5 | pages = 637–46 | date = Sep 2003 | pmid = 14517367 | doi = 10.1007/BF02703339 | s2cid = 27523830 | url = http://www.ias.ac.in/jbiosci/sep2003/637.pdf | url-status = dead | archive-url = https://web.archive.org/web/20070415213325/http://www.ias.ac.in/jbiosci/sep2003/637.pdf | archive-date = 15 April 2007 }} Here, the activated isoprene units are joined to make squalene and folded into a set of rings to make lanosterol.{{cite journal | vauthors = Schroepfer GJ | title = Sterol biosynthesis | journal = Annual Review of Biochemistry | volume = 50 | pages = 585–621 | year = 1981 | pmid = 7023367 | doi = 10.1146/annurev.bi.50.070181.003101 }} Lanosterol can then be converted into other steroids, such as cholesterol and ergosterol.{{cite journal | vauthors = Lees ND, Skaggs B, Kirsch DR, Bard M | title = Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae—a review | journal = Lipids | volume = 30 | issue = 3 | pages = 221–6 | date = Mar 1995 | pmid = 7791529 | doi = 10.1007/BF02537824 | s2cid = 4019443 }}

{{anchor|Pharmacological actions}}

Two classes of drugs target the mevalonate pathway: statins (like rosuvastatin), which are used to reduce elevated cholesterol levels,{{cite journal | vauthors = Kones R | title = Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease—a perspective | journal = Drug Design, Development and Therapy | volume = 4 | pages = 383–413 | date = December 2010 | pmid = 21267417 | pmc = 3023269 | doi = 10.2147/DDDT.S10812 | doi-access = free }} and bisphosphonates (like zoledronate), which are used to treat a number of bone-degenerative diseases.{{cite journal | vauthors = Roelofs AJ, Thompson K, Gordon S, Rogers MJ | title = Molecular mechanisms of action of bisphosphonates: current status | journal = Clinical Cancer Research | volume = 12 | issue = 20 Pt 2 | pages = 6222s–6230s | date = October 2006 | pmid = 17062705 | doi = 10.1158/1078-0432.CCR-06-0843 | s2cid = 9734002 | doi-access = }}

File:Steroidogenesis.svg pathways.{{cite journal | vauthors= Häggström M, Richfield D |year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|issn=2002-4436 |doi-access=free}} Changes in molecular structure from a precursor are highlighted in white.]]

{{See also|Steroidogenic enzyme|Steroidogenesis}}

Steroidogenesis is the biological process by which steroids are generated from cholesterol and changed into other steroids.{{cite journal | vauthors = Hanukoglu I | title = Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 43 | issue = 8 | pages = 779–804 | date = Dec 1992 | pmid = 22217824 | doi = 10.1016/0960-0760(92)90307-5 | s2cid = 112729 | url = https://zenodo.org/record/890723 | access-date = 20 April 2018 | archive-date = 26 April 2021 | archive-url = https://web.archive.org/web/20210426210129/https://zenodo.org/record/890723 | url-status = live }} The pathways of steroidogenesis differ among species. The major classes of steroid hormones, as noted above (with their prominent members and functions), are the progestogens, corticosteroids (corticoids), androgens, and estrogens. Human steroidogenesis of these classes occurs in a number of locations:

• Progestogens are the precursors of all other human steroids, and all human tissues which produce steroids must first convert cholesterol to pregnenolone. This conversion is the rate-limiting step of steroid synthesis, which occurs inside the mitochondrion of the respective tissue. It is catalyzed by the mitochondrial P450scc system.{{cite journal |vauthors=Hanukoglu I, Jefcoate CR |title=Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin |journal=J Biol Chem |volume=255 |issue=7 |pages=3057–61 |date=April 1980 |pmid=6766943 |doi=10.1016/S0021-9258(19)85851-9 |url=|doi-access=free }}{{cite journal |vauthors=Hanukoglu I, Privalle CT, Jefcoate CR |title=Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450scc and P-45011 beta |journal=J Biol Chem |volume=256 |issue=9 |pages=4329–35 |date=May 1981 |pmid=6783659 |doi=10.1016/S0021-9258(19)69437-8 |url=|doi-access=free }}
• Cortisol, corticosterone, aldosterone are produced in the adrenal cortex.
• Estradiol, estrone and progesterone are made primarily in the ovary, estriol in placenta during pregnancy, and testosterone primarily in the testes{{cite web | url=https://www.endocrine.org/patient-engagement/endocrine-library/hormones-and-endocrine-function/reproductive-hormones | title=Reproductive Hormones | date=24 January 2022 | access-date=12 February 2024 | archive-date=10 February 2024 | archive-url=https://web.archive.org/web/20240210160236/https://www.endocrine.org/patient-engagement/endocrine-library/hormones-and-endocrine-function/reproductive-hormones | url-status=live }}{{cite book | chapter-url=https://link.springer.com/chapter/10.1007/978-3-319-44558-8_1%22 | doi=10.1007/978-3-319-44558-8_1 | chapter=The Hypothalamic–Pituitary–Ovarian Axis and Oral Contraceptives: Regulation and Function | title=Sex Hormones, Exercise and Women | date=2017 | pages=1–17 | isbn=978-3-319-44557-1 | vauthors = Davis HC, Hackney AC }}{{cite encyclopedia|url=https://www.britannica.com/science/androgen|title=androgen|date=19 January 2024|access-date=12 February 2024|archive-date=29 January 2024|archive-url=https://web.archive.org/web/20240129083600/https://www.britannica.com/science/androgen|url-status=live}} (some testosterone may also be produced in the adrenal cortex).{{cite journal |vauthors=Oestlund I, Snoep J, Schiffer L, Wabitsch M, Arlt W, Storbeck KH |title=The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 catalyzes the activation of testosterone |journal=J Steroid Biochem Mol Biol |volume=236 |issue= |pages=106436 |date=February 2024 |pmid=38035948 |doi=10.1016/j.jsbmb.2023.106436|doi-access=free |hdl=10044/1/108335 |hdl-access=free }}
• Estradiol is converted from testosterone directly (in males), or via the primary pathway DHEA – androstenedione – estrone and secondarily via testosterone (in females).
• Stromal cells have been shown to produce steroids in response to signaling produced by androgen-starved prostate cancer cells.{{primary source inline|date=March 2017}}{{better source needed|date=March 2017}}
• Some neurons and glia in the central nervous system (CNS) express the enzymes required for the local synthesis of pregnenolone, progesterone, DHEA and DHEAS, de novo or from peripheral sources.{{citation needed|date=March 2017}}

{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}

In plants and bacteria, the non-mevalonate pathway (MEP pathway) uses pyruvate and glyceraldehyde 3-phosphate as substrates to produce IPP and DMAPP.{{cite journal | vauthors = Lichtenthaler HK | title = The 1-deoxy-d-xylulose-5-phosphate pathway of isoprenoid biosynthesis in plants | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 50 | pages = 47–65 | date = Jun 1999 | pmid = 15012203 | doi = 10.1146/annurev.arplant.50.1.47 }}

During diseases pathways otherwise not significant in healthy humans can become utilized. For example, in one form of congenital adrenal hyperplasia a deficiency in the 21-hydroxylase enzymatic pathway leads to an excess of 17α-Hydroxyprogesterone (17-OHP) – this pathological excess of 17-OHP in turn may be converted to dihydrotestosterone (DHT, a potent androgen) through among others 17,20 Lyase (a member of the cytochrome P450 family of enzymes), 5α-Reductase and 3α-Hydroxysteroid dehydrogenase.{{cite journal | pmc = 2910408 | pmid=20671993 | doi=10.1155/2010/625105 | volume=2010 | title=Nonclassic congenital adrenal hyperplasia | journal= International Journal of Pediatric Endocrinology| pages=1–11 | vauthors=Witchel SF, Azziz R| year=2010 | doi-access=free }}

Steroids are primarily oxidized by cytochrome P450 oxidase enzymes, such as CYP3A4. These reactions introduce oxygen into the steroid ring, allowing the cholesterol to be broken up by other enzymes into bile acids.{{cite journal | vauthors = Pikuleva IA | title = Cytochrome P450s and cholesterol homeostasis | journal = Pharmacology & Therapeutics | volume = 112 | issue = 3 | pages = 761–73 | date = Dec 2006 | pmid = 16872679 | doi = 10.1016/j.pharmthera.2006.05.014 }} These acids can then be eliminated by secretion from the liver in bile.{{cite journal | vauthors = Zollner G, Marschall HU, Wagner M, Trauner M | title = Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations | journal = Molecular Pharmaceutics | volume = 3 | issue = 3 | pages = 231–51 | year = 2006 | pmid = 16749856 | doi = 10.1021/mp060010s }} The expression of the oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids.{{cite journal | vauthors = Kliewer SA, Goodwin B, Willson TM | title = The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism | journal = Endocrine Reviews | volume = 23 | issue = 5 | pages = 687–702 | date = Oct 2002 | pmid = 12372848 | doi = 10.1210/er.2001-0038 | doi-access = free }} Steroid hormones, lacking the side chain of cholesterol and bile acids, are typically hydroxylated at various ring positions or oxidized at the 17 position, conjugated with sulfate or glucuronic acid and excreted in the urine.{{cite web | vauthors = Steimer T | title = Steroid Hormone Metabolism | url = http://www.gfmer.ch/Books/Reproductive_health/Steroid_hormone_metabolism.html | publisher = Geneva Foundation for Medical Education and Research | work = WHO Collaborating Centre in Education and Research in Human Reproduction | access-date = 27 March 2015 | archive-date = 17 February 2015 | archive-url = https://web.archive.org/web/20150217114802/http://www.gfmer.ch/Books/Reproductive_health/Steroid_hormone_metabolism.html | url-status = live }}

Steroid isolation, depending on context, is the isolation of chemical matter required for chemical structure elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram.{{cite book | veditors = Makin HL, Gower DB | title = Steroid analysis | vauthors = Makin HL, Honor JW, Shackleton CH, Griffiths WJ | chapter = General methods for the extraction, purification, and measurement of steroids by chromatography and mass spectrometry | pages = 163–282 | date = 2010 | publisher = Springer | location = Dordrecht; New York | isbn = 978-1-4020-9774-4}}{{page needed|date=May 2014}}

The methods of isolation to achieve the two scales of product are distinct, but include extraction, precipitation, adsorption, chromatography, and crystallization. In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS, are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample.

Structure determination refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography.{{rp|10–19}} Methods of analysis overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity.

Microbial catabolism of phytosterol side chains yields C-19 steroids, C-22 steroids, and 17-ketosteroids (i.e. precursors to adrenocortical hormones and contraceptives).{{cite journal | vauthors = Conner AH, Nagaoka M, Rowe JW, Perlman D | title = Microbial conversion of tall oil sterols to C19 steroids | journal = Applied and Environmental Microbiology | volume = 32 | issue = 2 | pages = 310–1 | date = August 1976 | pmid = 987752 | pmc = 170056 | doi = 10.1128/AEM.32.2.310-311.1976 | bibcode = 1976ApEnM..32..310C }}{{cite journal| vauthors = Hesselink PG, van Vliet S, de Vries H, Witholt B |title=Optimization of steroid side chain cleavage by Mycobacterium sp. in the presence of cyclodextrins|journal=Enzyme and Microbial Technology|date=1989|volume=11|issue=7|pages=398–404|doi=10.1016/0141-0229(89)90133-6}}{{cite book| vauthors = Sandow J, Jürgen E, Haring M, Neef G, Prezewowsky K, Stache U | chapter = Hormones|title=Ullmann's Encyclopedia of Industrial Chemistry|date=2000| publisher = Wiley-VCH Verlag GmbH & Co. KGaA|doi=10.1002/14356007.a13_089|isbn=978-3-527-30673-2}} The addition and modification of functional groups is key when producing the wide variety of medications available within this chemical classification. These modifications are performed using conventional organic synthesis and/or biotransformation techniques.{{cite journal| vauthors = Fried J, Thoma RW, Gerke JR, Herz JE, Donin MN, Perlman D |title=Microbiological Transformations of Steroids.1 I. Introduction of Oxygen at Carbon-11 of Progesterone|journal=Journal of the American Chemical Society|date=1952|volume=73|issue=23|pages=5933–5936|doi=10.1021/ja01143a033}}{{cite book| vauthors = Capek M, Oldrich H, Alois C |title=Microbial Transformations of Steroids|date=1966|publisher=Academia Publishing House of Czechoslovak Academy of Sciences|location=Prague|isbn=978-94-011-7605-7|doi=10.1007/978-94-011-7603-3|s2cid=13411462}}

The semisynthesis of steroids often begins from precursors such as cholesterol, phytosterols, or sapogenins.{{cite journal| vauthors = Marker RE, Rohrmann E |title=Sterols. LXXXI. Conversion of Sarsasa-Pogenin to Pregnanedial—3(α),20(α)|journal=Journal of the American Chemical Society|date=1939|volume=61|issue=12|pages=3592–3593|doi=10.1021/ja01267a513}} The efforts of Syntex, a company involved in the Mexican barbasco trade, used Dioscorea mexicana to produce the sapogenin diosgenin in the early days of the synthetic steroid pharmaceutical industry.{{cite web | url = https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html | title = Russell Marker Creation of the Mexican Steroid Hormone Industry | work = International Historic Chemical Landmark | publisher = American Chemical Society | access-date = 10 May 2014 | archive-date = 12 February 2020 | archive-url = https://web.archive.org/web/20200212065359/https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html | url-status = live }}

Some steroidal hormones are economically obtained only by total synthesis from petrochemicals (e.g. 13-alkyl steroids). For example, the pharmaceutical Norgestrel begins from methoxy-1-tetralone, a petrochemical derived from phenol.

A number of Nobel Prizes have been awarded for steroid research, including:

• 1927 (Chemistry) Heinrich Otto Wieland — Constitution of bile acids and sterols and their connection to vitamins{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1927/ | title = The Nobel Prize in Chemistry 1927 | publisher = The Nobel Foundation | access-date = 27 November 2013 | archive-date = 20 October 2012 | archive-url = https://web.archive.org/web/20121020171424/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1927/ | url-status = live }}
• 1928 (Chemistry) Adolf Otto Reinhold Windaus — Constitution of sterols and their connection to vitamins{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1928/ | title = The Nobel Prize in Chemistry 1928 | publisher = The Nobel Foundation | access-date = 27 November 2013 | archive-date = 17 October 2012 | archive-url = https://web.archive.org/web/20121017005100/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1928/ | url-status = live }}
• 1939 (Chemistry) Adolf Butenandt and Leopold Ružička — Isolation and structural studies of steroid sex hormones, and related studies on higher terpenes{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1939/ | title = The Nobel Prize in Chemistry 1939 | publisher = The Nobel Foundation | access-date = 27 November 2013 | archive-date = 20 October 2012 | archive-url = https://web.archive.org/web/20121020170744/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1939/ | url-status = live }}
• 1950 (Physiology or Medicine) Edward Calvin Kendall, Tadeus Reichstein, and Philip Hench — Structure and biological effects of adrenal hormones{{cite web | url = http://www.nobelprize.org/nobel_prizes/medicine/laureates/1950/ | title = The Nobel Prize in Physiology or Medicine 1950 | publisher = The Nobel Foundation | access-date = 27 November 2013 | archive-date = 19 October 2012 | archive-url = https://web.archive.org/web/20121019052608/http://www.nobelprize.org/nobel_prizes/medicine/laureates/1950/ | url-status = live }}
• 1965 (Chemistry) Robert Burns Woodward — In part, for the synthesis of cholesterol, cortisone, and lanosterol{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1965/ | title = The Nobel Prize in Chemistry 1965 | publisher = The Nobel Foundation | access-date = 1 December 2013 | archive-date = 6 November 2012 | archive-url = https://web.archive.org/web/20121106104006/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1965/ | url-status = live }}
• 1969 (Chemistry) Derek Barton and Odd Hassel — Development of the concept of conformation in chemistry, emphasizing the steroid nucleus{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1969/ | title = The Nobel Prize in Chemistry 1969 | publisher = The Nobel Foundation | access-date = 27 November 2013 | archive-date = 22 October 2012 | archive-url = https://web.archive.org/web/20121022170833/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1969/ | url-status = live }}
• 1975 (Chemistry) Vladimir Prelog — In part, for developing methods to determine the stereochemical course of cholesterol biosynthesis from mevalonic acid via squalene{{cite web | url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1975/ | title = The Nobel Prize in Chemistry 1975 | publisher = The Nobel Foundation | access-date = 1 December 2013 | archive-date = 20 October 2012 | archive-url = https://web.archive.org/web/20121020183933/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1975/ | url-status = live }}

{{Div col}}

• Adrenal gland
• Batrachotoxin
• List of steroid abbreviations
• List of steroids
• Membrane steroid receptor
• Pheromone
• Reverse cholesterol transport
• Steroidogenesis inhibitor
• Steroidogenic acute regulatory protein
• Steroidogenic enzyme

{{Div col end}}

{{reflist}}

{{refbegin|30em}}

• {{cite book | veditors = Russell CA, Roberts GK | vauthors = Russel CA | chapter = Organic Chemistry: Natural products, Steroids | title = Chemical History: Reviews of the Recent Literature | date = 2005| publisher = RSC Publ. | location = Cambridge | isbn = 978-0-85404-464-1 }}
• {{cite web | url = https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html | title = Russell Marker Creation of the Mexican Steroid Hormone Industry - Landmark - | publisher = American Chemical Society | date = 1999 | access-date = 10 May 2014 | archive-date = 12 February 2020 | archive-url = https://web.archive.org/web/20200212065359/https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/progesteronesynthesis.html | url-status = live }}
• {{cite book | vauthors = Lednicer D | title = Steroid Chemistry at a Glance | year = 2011 | publisher = Wiley | location = Hoboken | isbn = 978-0-470-66085-0 | doi = 10.1002/9780470973639 }} A concise history of the study of steroids.
• {{cite journal | vauthors = Yoder RA, Johnston JN | title = A case study in biomimetic total synthesis: polyolefin carbocyclizations to terpenes and steroids | journal = Chemical Reviews | volume = 105 | issue = 12 | pages = 4730–56 | date = Dec 2005 | pmid = 16351060 | pmc = 2575671 | doi = 10.1021/cr040623l}} A review of the history of steroid synthesis, especially biomimetic.
• {{cite journal | vauthors = Han TS, Walker BR, Arlt W, Ross RJ | title = Treatment and health outcomes in adults with congenital adrenal hyperplasia | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 2 | pages = 115–24 | date = Feb 2014 | pmid = 24342885 | doi = 10.1038/nrendo.2013.239 | s2cid = 6090764 }} Adrenal steroidogenesis pathway.
• {{cite book|veditors=Greep RO|title=Recent Progress in Hormone Research: Proceedings of the 1979 Laurentian Hormone Conference|chapter-url=https://books.google.com/books?id=eXXAAgAAQBAJ|chapter=Cortoic acids|pages=345–391|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-1956-1}}
• {{cite web | url = http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/basics/steroidogenesis.html | title = Steroidogenesis | vauthors = Bowen RA | date = 20 October 2001 | work = Pathophysiology of the Endocrine System | publisher = Colorado State University | url-status = dead | archive-url = https://web.archive.org/web/20090228213018/http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/basics/steroidogenesis.html | archive-date = 28 February 2009 }}

{{refend}}

{{Steroid classification}}

{{Terpenoids}}

{{Cholesterol metabolism intermediates}}

{{Steroids}}

{{Metabolism}}

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