adrenal cortex

The adrenal cortex comprises three main zones, or layers that are regulated by distinct hormones as noted below. This anatomic zonation can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics.{{cite book |author1=Whitehead, Saffron A. |author2=Nussey, Stephen |title=Endocrinology: an integrated approach |publisher=BIOS |location=Oxford |year=2001 |pages=122 |isbn=978-1-85996-252-7 }}

The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin–angiotensin–aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2).{{cite journal |vauthors=Curnow KM, Tusie-Luna MT, Pascoe L|display-authors=etal |title=The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex |journal=Mol. Endocrinol. |volume=5 |issue=10 |pages=1513–22 |date=October 1991 |pmid=1775135 |doi=10.1210/mend-5-10-1513|doi-access=free }}{{cite journal |vauthors=Zhou M, Gomez-Sanchez CE |title=Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant |journal=Biochem. Biophys. Res. Commun. |volume=194 |issue=1 |pages=112–7 |date=July 1993 |pmid=8333830 |doi=10.1006/bbrc.1993.1792}} Aldosterone is largely responsible for the long-term regulation of blood pressure.Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14 Aldosterone's effects are on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca²⁺ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca²⁺ channels entry.{{cite journal |vauthors=Hu C, Rusin CG, Tan Z, Guagliardo NA, Barrett PQ |title=Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators |journal=J. Clin. Invest. |volume=122 |issue=6 |pages=2046–53 |date=June 2012 |pmid=22546854 |doi=10.1172/JCI61996 |pmc=3966877}}

The secretion of aldosterone is also stimulated by adrenocorticotropic hormone (ACTH).{{cite journal | vauthors = Hanukoglu A, Fried D, Nakash I, Hanukoglu I | title = Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants. | journal = Eur J Endocrinol | volume = 133 | issue = 5 | pages = 552–6 |date=Nov 1995 | doi = 10.1530/eje.0.1330552 | pmid = 7581984 | s2cid = 44439040 }}

The cells of the zona glomerulosa do not express 11β-hydroxylase and 17α-hydroxylase. This is the reason zona glomerulosa cannot synthesize cortisol, corticosterone, or sex hormones (androgens).{{Cite book |last=Barrett |first=Kim E. |url=https://www.worldcat.org/oclc/1076268769 |title=Ganong's review of medical physiology |date=2019 |others=Susan M. Barman, Heddwen L. Brooks, Jason X.-J. Yuan, William F. Preceded by: Ganong |isbn=9781260122404 |edition=26th |location=[New York] |pages=337 |oclc=1076268769}}

The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors{{cite journal |vauthors=Ehrhart-Bornstein M, Hilbers U |title=Neuroendocrine properties of adrenocortical cells |journal=Horm. Metab. Res. |volume=30 |issue=6–7 |pages=436–9 |year=1998 |pmid=9694576 |doi=10.1055/s-2007-978911|s2cid=260169208 |url=https://zenodo.org/record/1236012 }}{{cite journal |vauthors=Lefebvre H, Cartier D, Duparc C|display-authors=etal |title=Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=3 |pages=1211–6 |date=March 2002 |pmid=11889190 |doi=10.1210/jcem.87.3.8327|doi-access= }}{{cite journal |vauthors=Ye P, Mariniello B, Mantero F, Shibata H, Rainey WE |title=G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism |journal=J. Endocrinol. |volume=195 |issue=1 |pages=39–48 |date=October 2007 |pmid=17911395 |doi=10.1677/JOE-07-0037|doi-access=free }} and it was suggested that the expression of proteins like the neuronal cell adhesion molecule (NCAM) in the cells of the zona glomerulosa reflects the regenerative feature of these cells, which would lose NCAM immunoreactivity after moving to the zona fasciculata.{{cite journal |vauthors=Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lübke C, Ehrhart-Bornstein M |title=Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells |journal=Endocrinology |volume=139 |issue=2 |pages=772–80 |date=February 1998 |pmid=9449652 |doi=10.1210/endo.139.2.5740|doi-access=free }} However, together with other data on neuroendocrine properties of zona glomerulosa cells, NCAM expression may reflect a neuroendocrine differentiation of these cells.

Situated between the glomerulosa and reticularis, the cells of the zona fasciculata synthesize and secrete glucocorticoids (such as 11-deoxycorticosterone, corticosterone, and cortisol), as well as small amounts of adrenal androgens and estrogens.{{Cite book |last=Hall |first=John E. |url=https://www.worldcat.org/oclc/1129099861 |title=Guyton and Hall textbook of medical physiology |date=2021 |others=Michael E. Hall |isbn=978-0-323-59712-8 |edition=14th |location=Philadelphia, PA |pages=956 |oclc=1129099861}} The zona fasciculata has more 3β-hydroxysteroid dehydrogenase activity than the zona reticularis. Therefore, the zona fasciculata makes more 11-deoxycorticosterone, corticosterone, and cortisol. The major hormone that stimulates cortisol secretion in humans is the ACTH that is released from the anterior pituitary. It has been shown that the steroidogenic capacity of the zona fasciculata increases during illness in infants.

The innermost cortical layer, the zona reticularis, produces adrenal androgens, as well as small amounts of estrogens and some glucocorticoids. The zona reticularis has more of the cofactors required for the 17,20-lyase activity of 17α-hydroxylase than zona fasciculata. Therefore, the zona reticularis makes more androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans. The secretion of DHEAS is also stimulated by ACTH.

File:Adrenal Steroids Pathways - edited.svg

The precursor of steroids synthesized in the adrenal cortex is cholesterol that is stored in vesicles. Cholesterol can be synthesized de novo in the adrenal cortex. Yet, the major source of cholesterol appears to be cholesterol that is taken up with circulating lipoproteins.

{{cite journal| vauthors=London E, Wassif CA, Horvath A, Tatsi C, Angelousi A, Karageorgiadis AS, Porter FD, Stratakis CA| title=Cholesterol Biosynthesis and Trafficking in Cortisol-Producing Lesions of the Adrenal Cortex. | journal=J Clin Endocrinol Metab | year= 2015 | volume= 100 | issue= 10 | pages= 3660–7 | pmid=26204136 | doi=10.1210/jc.2015-2212 | pmc=4596036 }}

The steps up to this point occur in many steroid-producing tissues. Subsequent steps to generate aldosterone and cortisol, however, primarily occur in the adrenal cortex:

• Progesterone → (hydroxylation at C21) → 11-Deoxycorticosterone → (two further hydroxylations at C11 and C18) → Aldosterone
• Progesterone → (hydroxylation at C17) → 17-alpha-hydroxyprogesterone → (hydroxylation at C21) → 11-Deoxycortisol → (hydroxylation at C11) → Cortisol

File:Adrenal steroid hormone synthesis.png

The adrenal cortex produces a number of different corticosteroid hormones.

{{Main|Mineralocorticoids}}

The primary mineralocorticoid, aldosterone, is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely responsible for the long-term regulation of blood pressure. Aldosterone effects on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca²⁺ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca²⁺ channels entry.

{{Main|Glucocorticoids}}

Glucocorticoids are produced mainly in the zona fasciculata.

Glucocorticoids are steroid hormones that are necessary for life.{{Cite journal |last1=Cain |first1=Derek W. |last2=Cidlowski |first2=John A. |date=2017-02-13 |title=Immune regulation by glucocorticoids |journal=Nature Reviews Immunology |language=en |volume=17 |issue=4 |pages=233–247 |doi=10.1038/nri.2017.1 |issn=1474-1733 |pmc=9761406 |pmid=28192415}} They play a role in numerous physiological responses including; metabolism, immune response, mood, cognitive functions, cardiovascular function, and reproduction.{{Cite journal |last1=Timmermans |first1=Steven |last2=Souffriau |first2=Jolien |last3=Libert |first3=Claude |date=2019-07-04 |title=A General Introduction to Glucocorticoid Biology |journal=Frontiers in Immunology |language=English |volume=10 |page=1545 |doi=10.3389/fimmu.2019.01545 |doi-access=free |issn=1664-3224 |pmc=6621919 |pmid=31333672}} Glucocorticoids are also widely prescribed as medication to treat numerous conditions such as autoimmune diseases and lymphoproliferative diseases. {{Cite journal |last1=CHARMANDARI |first1=EVANGELIA |last2=KINO |first2=TOMOSHIGE |last3=CHROUSOS |first3=GEORGE P. |date=June 2004 |title=Glucocorticoids and Their Actions: An Introduction |url=https://login.libaccess.sjlibrary.org/login?qurl=https://doi.org%2f10.1196%2fannals.1321.001 |journal=Annals of the New York Academy of Sciences |language=en |volume=1024 |issue=1 |pages=1–8 |doi=10.1196/annals.1321.001 |pmid=15265770 |bibcode=2004NYASA1024....1C |issn=0077-8923|url-access=subscription }} The main glucocorticoid in humans is cortisol.{{Cite journal |last1=Manenschijn |first1=Laura |last2=van den Akker |first2=Erica L. T. |last3=Lamberts |first3=Steven W. J. |last4=van Rossum |first4=Elisabeth F. C. |date=October 2009 |title=Clinical features associated with glucocorticoid receptor polymorphisms. An overview |url=https://pubmed.ncbi.nlm.nih.gov/19906240/ |journal=Annals of the New York Academy of Sciences |volume=1179 |pages=179–198 |doi=10.1111/j.1749-6632.2009.05013.x |issn=1749-6632 |pmid=19906240}}

{{Main|Androgens}}

They are produced mainly in the zona reticularis. The most important androgens include:

• Testosterone: a hormone with a wide variety of effects, ranging from enhancing muscle mass and stimulation of cell growth to the development of the secondary sex characteristics.
• Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors.
• Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of estrone.
• Dehydroepiandrosterone (DHEA): It is the primary precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone. The reticularis also produces DHEA-sulfate due to the actions of a sulfotransferase, SULT2A1.{{cite journal |vauthors=Rainey WE, Nakamura Y |title=Regulation of the adrenal androgen biosynthesis |journal=J. Steroid Biochem. Mol. Biol. |volume=108 |issue=3–5 |pages=281–6 |date=February 2008 |pmid=17945481 |pmc=2699571 |doi=10.1016/j.jsbmb.2007.09.015}}

File:Adrenal Cortex Pathology.png

• Adrenal insufficiency (e.g. due to Addison's disease)
• Cushing's syndrome
• Cushing's disease
• Conn's syndrome
• Adrenocortical carcinoma

• Adrenarche
• Adrenopause

{{Reflist}}

• {{SUNYAnatomyLabs|40|04|02|03}} – "Posterior Abdominal Wall: Blood Supply to the Suprarenal Glands"
• {{MedicalMnemonics|180|2201|412}}
• {{BUHistology|14502loa}}

{{Adrenal gland}}

{{Authority control}}

{{DEFAULTSORT:Adrenal Cortex}}

Category:Adrenal gland

Category:Endocrine system anatomy