progesterone receptor A
{{Short description|Isoform of the progesterone receptor}}
The progesterone receptor A (PR-A) is one of three known isoforms of the progesterone receptor (PR), the main biological target of the endogenous progestogen sex hormone progesterone.{{cite journal | vauthors = Jacobsen BM, Horwitz KB | title = Progesterone receptors, their isoforms and progesterone regulated transcription | journal = Mol. Cell. Endocrinol. | volume = 357 | issue = 1–2 | pages = 18–29 | year = 2012 | pmid = 21952082 | pmc = 3272316 | doi = 10.1016/j.mce.2011.09.016 }}{{cite journal | vauthors = Scarpin KM, Graham JD, Mote PA, Clarke CL | title = Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression | journal = Nucl Recept Signal | volume = 7 | pages = e009 | year = 2009 | pmid = 20087430 | pmc = 2807635 | doi = 10.1621/nrs.07009 }} The other isoforms of the PR include the PR-B and PR-C.
File:Progesterone Receptor Isoform A.png
PR-A is 164 residues shorter than PR-B in humans{{Cite journal |last1=Graham |first1=J Dinny |last2=Clarke |first2=Christine L |date=October 2002 |title=Progesterone receptors - animal models and cell signaling in breast cancer: Expression and transcriptional activity of progesterone receptor A and progesterone receptor B in mammalian cells |journal=Breast Cancer Research |language=en |volume=4 |issue=5 |pages=187–190 |doi=10.1186/bcr450 |doi-access=free |issn=1465-542X |pmc=138742 |pmid=12223122}} and anywhere from 128-165 residues shorter in other organisms.{{Cite journal |last=Conneely |first=O |date=November 2000 |title=Progesterone receptors in reproduction: functional impact of the A and B isoforms |url=https://linkinghub.elsevier.com/retrieve/pii/S0039128X0000115X |journal=Steroids |volume=65 |issue=10–11 |pages=571–577 |doi=10.1016/S0039-128X(00)00115-X|pmid=11108861 |url-access=subscription }} Each isoform binds its natural ligand, progesterone, but also demonstrates the ability to bind a number of other agonists including norethindrone, a synthetic progestin.{{Cite journal |last1=Madauss |first1=Kevin P. |last2=Deng |first2=Su-Jun |last3=Austin |first3=Robert J. H. |last4=Lambert |first4=Millard H. |last5=McLay |first5=Iain |last6=Pritchard |first6=John |last7=Short |first7=Steven A. |last8=Stewart |first8=Eugene L. |last9=Uings |first9=Ian J. |last10=Williams |first10=Shawn P. |date=2004-06-01 |title=Progesterone Receptor Ligand Binding Pocket Flexibility: Crystal Structures of the Norethindrone and Mometasone Furoate Complexes |url=https://pubs.acs.org/doi/10.1021/jm030640n |journal=Journal of Medicinal Chemistry |language=en |volume=47 |issue=13 |pages=3381–3387 |doi=10.1021/jm030640n |pmid=15189034 |issn=0022-2623|url-access=subscription }}
File:Dimerized Progesterone Receptor Bound to Norethindrone 20250509.png
Expression and overexpression
PR-A and PR-B are generally expressed in equal ratios, but PR-A is expressed in larger amounts in uterine stromal cells normally.{{Cite journal |last1=Bulun |first1=Serdar E. |last2=Cheng |first2=You-Hong |last3=Yin |first3=Ping |last4=Imir |first4=Gonca |last5=Utsunomiya |first5=Hiroki |last6=Attar |first6=Erkut |last7=Innes |first7=Joy |last8=Julie Kim |first8=J. |date=March 2006 |title=Progesterone resistance in endometriosis: Link to failure to metabolize estradiol |url=https://linkinghub.elsevier.com/retrieve/pii/S0303720705004442 |journal=Molecular and Cellular Endocrinology |language=en |volume=248 |issue=1–2 |pages=94–103 |doi=10.1016/j.mce.2005.11.041|pmid=16406281 |url-access=subscription }} A spike in PR-A expression in the myometrium has been observed to initiate parturition in placental mammals.{{Cite journal |last1=Cope |first1=Dominique |last2=Monsivais |first2=Diana |date=2022-04-27 |title=Progesterone Receptor Signaling in the Uterus Is Essential for Pregnancy Success |journal=Cells |language=en |volume=11 |issue=9 |pages=1474 |doi=10.3390/cells11091474 |doi-access=free |issn=2073-4409 |pmc=9104461 |pmid=35563781}}
PR-A is the isoform most commonly observed to be overexpressed in human breast cancer. Currently PR is estimated by immunohistochemistry and earlier was quantified by standardized radio-ligand binding assays developed by New England Nuclear and Wittliff.Fisher, B., Redmond, C., Brown, A., Wickerham, D. L., Wolmark, N., Allegra, J. C., Escher, G., Lippman, M., Savlov, E., Wittliff, J. L. and Fisher, E. R. et al. Influence of Tumor Estrogen and Progesterone Receptor Levels on the Response to Tamoxifen and Chemotherapy in Primary Breast Cancer. J. Clin. Oncol., 1:227-241, 1983. https://pubmed.ncbi.nlm.nih.gov/6366135/ Patients with PR-A rich carcinomas, as opposed to patients with PR-B rich carcinomas, have faster recurrence rates.{{Cite journal |last1=Timmermans-Sprang |first1=Elpetra P. M. |last2=Gracanin |first2=Ana |last3=Mol |first3=Jan A. |date=2017-04-13 |title=Molecular Signaling of Progesterone, Growth Hormone, Wnt, and HER in Mammary Glands of Dogs, Rodents, and Humans: New Treatment Target Identification |journal=Frontiers in Veterinary Science |volume=4 |page=53 |doi=10.3389/fvets.2017.00053 |doi-access=free |issn=2297-1769 |pmc=5389977 |pmid=28451590}}
See also
References
{{Reflist|2}}
{{Transcription factors|g2}}
{{Progesterone receptor modulators}}
Category:Intracellular receptors
Category:Transcription factors
{{receptor-stub}}