Progesterone receptor

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Progesterone receptor
PDB rendering based on 1a28.
Identifiers
Symbol(s)	PGR; NR3C3; PR
External IDs	OMIM: 607311 MGI: 97567 Homologene: 713
Gene ontology Molecular Function: • transcription factor activity • steroid hormone receptor activity • steroid binding • protein binding • zinc ion binding • lipid binding • sequence-specific DNA binding • metal ion binding Cellular Component: • nucleus Biological Process: • ovulation (sensu Mammalia) • transcription • regulation of transcription, DNA-dependent • transcription from RNA polymerase II promoter • signal transduction • cell-cell signaling • mammary gland development • regulation of epithelial cell proliferation • progesterone receptor signaling pathway
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	5241	18667
Ensembl	ENSG00000082175	ENSMUSG00000031870
Uniprot	P06401	Q8BW69
Refseq	NM_000926 (mRNA) NP_000917 (protein)	NM_008829 (mRNA) NP_032855 (protein)
Location	Chr 11: 100.41 - 100.51 Mb	Chr 9: 8.86 - 8.93 Mb
Pubmed search	[2]	[3]

WikiDoc Resources for Progesterone receptor
Articles
Most recent articles on Progesterone receptor Most cited articles on Progesterone receptor Review articles on Progesterone receptor Articles on Progesterone receptor in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Progesterone receptor Images of Progesterone receptor Photos of Progesterone receptor Podcasts & MP3s on Progesterone receptor Videos on Progesterone receptor
Evidence Based Medicine
Cochrane Collaboration on Progesterone receptor Bandolier on Progesterone receptor TRIP on Progesterone receptor
Clinical Trials
Ongoing Trials on Progesterone receptor at Clinical Trials.gov Trial results on Progesterone receptor Clinical Trials on Progesterone receptor at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Progesterone receptor NICE Guidance on Progesterone receptor NHS PRODIGY Guidance FDA on Progesterone receptor CDC on Progesterone receptor
Books
Books on Progesterone receptor
News
Progesterone receptor in the news Be alerted to news on Progesterone receptor News trends on Progesterone receptor
Commentary
Blogs on Progesterone receptor
Definitions
Definitions of Progesterone receptor
Patient Resources / Community
Patient resources on Progesterone receptor Discussion groups on Progesterone receptor Patient Handouts on Progesterone receptor Directions to Hospitals Treating Progesterone receptor Risk calculators and risk factors for Progesterone receptor
Healthcare Provider Resources
Symptoms of Progesterone receptor Causes & Risk Factors for Progesterone receptor Diagnostic studies for Progesterone receptor Treatment of Progesterone receptor
Continuing Medical Education (CME)
CME Programs on Progesterone receptor
International
Progesterone receptor en Espanol Progesterone receptor en Francais
Businness
Progesterone receptor in the Marketplace Patents on Progesterone receptor
Experimental / Informatics
List of terms related to Progesterone receptor

The progesterone receptor (PR) also known as NR3C3 (nuclear receptor subfamily 3, group C, member 3), is an intracellular steroid receptor that specifically binds progesterone. PR is encoded by a single gene PGR residing on chromosome 11q22, it has two main forms, A and B, that differ in their molecular weight.^[1][1][1]

Structure

Like all steroid receptors, the progesterone receptor has an amino and a carboxyl terminal, and between them the regulatory domain, a DNA binding domain, the hinge section, and the hormone binding domain. A special transcription activation function (TAF), called TAF-3, is present in the progesterone receptor-B, in a B-upstream segment (BUS) at the amino acid terminal. This segment is not present in the receptor-A.

Isoforms

As demonstrated in progesterone receptor-deficient mice, the physiological effects of progesterone depend completely on the presence of the human progesterone receptor (hPR), a member of the steroid-receptor superfamily of nuclear receptors. The single-copy human (hPR) gene uses separate promoters and translational start sites to produce two isoforms, hPR-A and -B, which are identical except for an additional 165 amino acids present only in the N terminus of hPR-B.^[1] Although hPR-B shares many important structural domains as hPR-A, they are in fact two functionally distinct transcription factors, mediating their own response genes and physiological effects with little overlap. Selective ablation of PR-A in a mouse model, resulting in exclusive production of PR-B, unexpectedly revealed that PR-B contributes to, rather than inhibits, epithelial cell proliferation both in response to estrogen alone and in the presence of progesterone and estrogen. These results suggest that in the uterus, the PR-A isoform is necessary to oppose estrogen-induced proliferation as well as PR-B-dependent proliferation.

Functional Polymorphisms

The Immaculata De Vivo laboratory at the Harvard Medical School has identified six variable sites, including four polymorphisms in the hPR gene and five common haplotypes. One promoter region polymorphism, +331G/A, creates a unique transcription start site. Biochemical assays showed that the +331G/A polymorphism increases transcription of the PR gene, favoring production of hPR-B in an Ishikawa endometrial cancer cell line.

Several studies have now shown no association between progesterone receptor gene +331G/A polymorphisms and breast or endometrial cancers.^[1][1] However, these follow-up studies lacked the sample size and statistical power to make any definitive conclusions, due to the rarity of the +331A SNP. It is currently unknown which if any polymorphisms in this receptor is of significance to cancer.

Function

Estrogen is necessary to induce the progesterone receptors. When no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a structural change that removes the inhibitory action. Progesterone antagonists prevent the structural reconfiguration.

After progesterone binds to the receptor, restructuring with dimerization follows and the complex enters the nucleus and binds to DNA. There transcription takes place, resulting in formation of messenger RNA that activates cytoplasmatic ribosomes to produce specific proteins.

See also

• Selective progesterone receptor modulator

Further reading

References

External links

• MeSH Progesterone+Receptors

v • d • e WikiDoc Research Resources for Progesterone receptor
Articles on Progesterone receptor	Most recent articles on Progesterone receptor • Most cited articles on Progesterone receptor • Review articles on Progesterone receptor • Articles on Progesterone receptor in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Progesterone receptor	Powerpoint slides on Progesterone receptor • Images of Progesterone receptor • Photos of Progesterone receptor • Podcasts & MP3s on Progesterone receptor • Videos on Progesterone receptor
Evidence Based Medicine Regarding Progesterone receptor	Cochrane Collaboration on Progesterone receptor • Bandolier on Progesterone receptor • TRIP on Progesterone receptor
Cost Effectiveness of Progesterone receptor	Cost Effectiveness of Progesterone receptor
Clinical Trials Involving Progesterone receptor	Ongoing Trials on Progesterone receptor at Clinical Trials.gov • Trial results on Progesterone receptor • Clinical Trials on Progesterone receptor at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Progesterone receptor	US National Guidelines Clearinghouse on Progesterone receptor • NICE Guidance on Progesterone receptor • NHS PRODIGY Guidance • FDA on Progesterone receptor • CDC on Progesterone receptor
Textbook Information on Progesterone receptor	Books and Textbook Information on Progesterone receptor
Pharmacology Resources on Progesterone receptor	Dosing of Progesterone receptor • Drug interactions with Progesterone receptor • Side effects of Progesterone receptor • Allergic reactions to Progesterone receptor • Overdose information on Progesterone receptor • Carcinogenicity information on Progesterone receptor • Progesterone receptor in pregnancy • Pharmacokinetics of Progesterone receptor •
Genetics, Pharmacogenomics, and Proteinomics of Progesterone receptor	Genetics of Progesterone receptor • Pharmacogenomics of Progesterone receptor • Proteomics of Progesterone receptor
Newstories on Progesterone receptor	Progesterone receptor in the news • Be alerted to news on Progesterone receptor • News trends on Progesterone receptor
Commentary on Progesterone receptor	Blogs on Progesterone receptor
Patient Resources on Progesterone receptor	Patient resources on Progesterone receptor • Discussion groups on Progesterone receptor • Patient Handouts on Progesterone receptor • Directions to Hospitals Treating Progesterone receptor • Risk calculators and risk factors for Progesterone receptor
Healthcare Provider Resources on Progesterone receptor	Symptoms of Progesterone receptor • Causes & Risk Factors for Progesterone receptor • Diagnostic studies for Progesterone receptor • Treatment of Progesterone receptor
Continuing Medical Education (CME) Programs on Progesterone receptor	CME Programs on Progesterone receptor
International Resources on Progesterone receptor	Progesterone receptor en Espanol • Progesterone receptor en Francais
Business Resources on Progesterone receptor	Progesterone receptor in the Marketplace • Patents on Progesterone receptor
Informatics Resources on Progesterone receptor	List of terms related to Progesterone receptor

v • d • e Transcription factors and intracellular receptors
(1) Basic domains	(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1 (1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1 (1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2) (1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger DNA-binding domains	(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP) (2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6) (2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33) (2.4) Cys6 HIVEP1
(3) Helix-turn-helix domains	(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) (3.2) Paired box PAX (1, 2, 3, 4, 5, 6, 7, 8, 9) (3.3) Fork head / winged helix E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3) (3.4) Heat Shock Factors HSF1 (3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB (3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with minor groove contacts	(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4) (4.2) STAT STAT (1, 2, 3, 4, 5, 6) (4.3) p53 p53 (4.4) MADS box Mef2 (A, B, C, D) • SRF (4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1 (4.10) Cold-shock domain CSDA
(0) Other transcription factors	(0.2) HMGI(Y) HMGA (1, 2) (0.3) Pocket domain Rb • RBL1 • RBL2 (0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD

v • d • e Sex hormones and related agents (primarily G03, also L02, H01C) - human endogenous in CAPS
Progestogens: (receptor)	PROGESTERONE,Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone Selective progesterone receptor modulator: Asoprisnil, CDB-4124 Antiprogestogen: Mifepristone
Androgens: (receptor)	TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, (see also anabolic steroids) Antiandrogens: Bicalutamide, Cyproterone,