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PGR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4OAR, 1A28, 1E3K, 1SQN, 1SR7, 1ZUC, 2C7A, 2OVH, 2OVM, 2W8Y, 3D90, 3G8O, 3HQ5, 3KBA, 3ZR7, 3ZRA, 3ZRB, 4A2J, 4APU, 5CC0
Identifiers
Aliases	PGR, NR3C3, PR, progesterone receptor
External IDs	MGI: 97567 HomoloGene: 713 GeneCards: PGR
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q22.1 Start 101,029,624 bp[1] End 101,130,524 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A1 Start 8,899,833 bp[2] End 8,968,611 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • ATPase binding • zinc ion binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • metal ion binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • steroid hormone receptor activity • steroid binding • protein binding • enzyme binding • receptor binding • lipid binding • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • identical protein binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Cellular component • cytoplasm • membrane • nucleoplasm • mitochondrial outer membrane • mitochondrion • cell nucleus • cytosol Biological process • regulation of transcription, DNA-templated • cell-cell signaling • negative regulation of gene expression • transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • signal transduction • steroid hormone mediated signaling pathway • positive regulation of transcription from RNA polymerase II promoter • ovulation from ovarian follicle • epithelial cell maturation • mammary gland development • paracrine signaling • lung alveolus development • regulation of epithelial cell proliferation • progesterone receptor signaling pathway • tertiary branching involved in mammary gland duct morphogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5241	18667
Ensembl	ENSG00000082175	ENSMUSG00000031870
UniProt	P06401	Q00175
RefSeq (mRNA)	NM_000926 NM_001202474 NM_001271161 NM_001271162	NM_008829
RefSeq (protein)	NP_000917 NP_001189403 NP_001258090 NP_001258091	NP_032855
Location (UCSC)	Chr 11: 101.03 – 101.13 Mb	Chr 9: 8.9 – 8.97 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.

In humans, PR is encoded by a single PGR gene residing on chromosome 11q22,^[5][6][7] it has two isoforms, PR-A and PR-B, that differ in their molecular weight.^[8][9][10] The PR-B is the positive regulator of the effects of progesterone, while PR-A serve to antagonize the effects of PR-B.^[11]

Function

Progesterone 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 is translated by ribosomes to produce specific proteins.

Structure

In common with other steroid receptors, the progesterone receptor has a N-terminal regulatory domain, a DNA binding domain, a hinge section, and a C-terminal ligand 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.^[12] Although hPR-B shares many important structural domains with 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

Six variable sites, including four polymorphisms and five common haplotypes have been identified in the human PR gene .^[13] 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.^[14]

Several studies have now shown no association between progesterone receptor gene +331G/A polymorphisms and breast or endometrial cancers.^[15][16] 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 are of significance to cancer.

Biological role

Knockout mice of the PR have been found to have severely impaired lobuloalveolar development of the mammary glands^[17] as well as delayed but otherwise normal mammary ductal development at puberty.^[18][19]

Ligands

Agonists

• 
  Endogenous progestogens (e.g., progesterone)


• 
  Synthetic progestogens (e.g., norethisterone, levonorgestrel, medroxyprogesterone acetate, megestrol acetate, dydrogesterone, drospirenone)

Mixed

• 
  Selective progesterone receptor modulators (e.g., ulipristal acetate, telapristone acetate, vilaprisan, asoprisnil, asoprisnil ecamate)^[20]
  

Antagonists

• 
  Antiprogestogens (e.g., mifepristone, aglepristone, onapristone, lonaprisan, lilopristone, toripristone)^[20]
  

Interactions

Progesterone receptor has been shown to interact with:

• 
  KLF9,^[21]
  


• 
  Nuclear receptor co-repressor 2,^[22] and


• 
  UBE3A.^[23]
  

See also

• Membrane progesterone receptor


• Selective progesterone receptor modulator


• Phytoprogestogen

References

Further reading

External links

• 
  Progesterone+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)