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Information about Progesterone Receptor

Progesterone Receptor
Identifiers
SymbolPGR
Entrez5241
HUGO8910
OMIM607311
RefSeqNM_000926
UniProtP06401
Other data
LocusChr. 11 q22-23


The progesterone receptor is an intracellular steroid receptor that specifically binds progesterone. Expressed by a single gene (chromosome 11q22), it has two main forms, A and B, that differ in their molecular weight.[1][2][3]

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.[4] 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.[5][6] 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

References

1. ^ Gadkar-Sable S, Shah C, Rosario G, Sachdeva G, Puri C (2005). "Progesterone receptors: various forms and functions in reproductive tissues". Front. Biosci. 10: 2118-30. DOI:10.2741/1685. PMID 15970482. 
2. ^ Kase, Nathan G.; Speroff, Leon; Glass, Robert L. (1999). Clinical gynecologic endocrinology and infertility. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-683-30379-1. 
3. ^ Fritz, Marc A.; Speroff, Leon (2005). Clinical gynecologic endocrinology and infertility. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-4795-3. 
4. ^ Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (1990). "Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B". EMBO J. 9 (5): 1603-14. PMID 2328727. 
5. ^ Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (2004). "No association between the progesterone receptor gene +331G/A polymorphism and breast cancer". Cancer Epidemiol. Biomarkers Prev. 13 (6): 1084-5. PMID 15184270. 
6. ^ Dossus L, Canzian F, Kaaks R, Boumertit A, Weiderpass E (2006). "No association between progesterone receptor gene +331G/A polymorphism and endometrial cancer". Cancer Epidemiol. Biomarkers Prev. 15 (7): 1415-6. DOI:10.1158/1055-9965.EPI-06-0215. PMID 16835347. 

External links

 •  • [ e]
Transcription factors and intracellular receptors
General transcription factorsTFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH
Basic-helix-loop-helixAhR - BMAL-CLOCK - E2F - HIF - Myc - Pax (PAX3, PAX6) - Twist - Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6)
Basic leucine zipperC/EBP - CREB - AP-1 (c-Fos, c-Jun) - Activating transcription factor
Basic helix-loop-helix leucine zipperMITF - SREBP
Nuclear receptorssubfamily 1 (Thyroid hormone, CAR, FXR, LXR, PPAR, PXR, RAR, ROR, Rev-ErbA, VDR) -
subfamily 2 (COUP-TF, Ear-2, HNF4, PNR, RXR, Testicular receptor, TLX) -
subfamily 3/Steroid hormone (Estrogen, Estrogen related, Glucocorticoid, Mineralocorticoid, Progesterone, Androgen) -
subfamily 4 (NGFIB, NURR1, NOR1) - subfamily 5 (SF1, LRH-1) - subfamily 6 (GCNF) - subfamily 0 (DAX1, SHP)
Winged-helix transcription factorsFOX proteins (FOXP2, FOXP3)
Zinc finger/proteinGli1 - Gli2 - Gli3 - KlF (Sp1) - Zbtb7 - Zif268
Other familiesCAP - CBF (RUNX1, RUNX2) - GATA (GATA1) - NANOG - NF-kB - Rho/Sigma - R-SMAD - Sox2 - POU domain (PIT-1, BRN-3, Octamer transcription factor: 2, 4) - STAT (1, 2, 3, 4, 5, 6)
 •  • [ e]
Sex hormones and related agents (primarily G03, also L02, H01C) - human endogenous in CAPS
Progestogens:
(receptor)		PROGESTERONE, 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, Flutamide, Nilutamide, Spironolactone
Estrogens:
(receptor)		ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate
Selective estrogen receptor modulator: Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene
Aromatase inhibitor: Aminogluthetimide, Anastrozole, Exemestane, Formestane, Letrozole, Vorozole
Gonadotropins:
(FSHR/LHCGR)'		ovulation stim.: Clomifene, Urofollitropin
Antigonadotropins:'' Danazol, Gestrinone
GnRH:
(receptor)		agonist: Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin
antagonist: Abarelix, Cetrorelix, Ganirelix
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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Steroid hormone receptors are intracellular receptors (typically cytoplasmic) that perform signal transduction for steroid hormones. Steroid hormone receptors are part of the nuclear receptor family that include a group of homologous structured receptors (type II receptors) that
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Progesterone is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Progesterone belongs to a class of hormones called progestogens, and is the major naturally occurring human
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Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division.]] A chromosome is a single large macromolecule of DNA, and constitutes a physically organized form of DNA in a cell.
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In the field of molecular biology, nuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of hormones and certain other molecules.
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Estrogens (alternative spellings: oestrogens or œstrogens) are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone.
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Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. So to say, it is the transfer of genetic information from DNA into RNA.
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dimer refers to a molecule composed of two identical subunits or monomers linked together.

Chemistry

The molecules in a dimer are connected by covalent bonds or weaker interactions such as hydrogen bonds.
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Messenger Ribonucleic Acid (mRNA) is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes.
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A ribosome is a small, dense, functional structure found in most known cells that assemble proteins and polypeptides used in cell division. It catalyses the assembly of individual amino acids into polypeptide chains by reading messenger RNAs and binding amino acids that are
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A selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. A characteristic that distinguishes such substances from receptor full agonists (such as progesterone) and full antagonists (such as RU 486) is that their action differs in
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digital object identifier (or DOI) is a permanent identifier given to a document, which is not related to its current location. A typical use of a DOI is to give a scientific paper or article a unique identifying number that can be used by anyone to locate details of the paper, and
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Intracellular receptors are receptors located inside the cell rather than on its cell membrane. Examples are the class of nuclear receptors located in the cell nucleus and the IP3 receptor located on the endoplasmic reticulum.
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General transcription factors (GTF's) are protein transcription factors which have been shown to be important in the transcription of class II genes to mRNA templates. Many of them are involved in the formation of a preinitiation complex, which, together with RNA polymerase II,
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Identifiers
Symbol GTF2A2

Entrez 2958
HUGO 4647
OMIM 600519

RefSeq NM_004492
UniProt P52657
Other data

Locus Chr. 15 q21.3

Transcription factor TFIIA
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basic-helix-loop-helix (bHLH) is a protein structural motif that characterizes a family of transcription factors.

Structure

The motif is characterized by two α helices connected by a loop.
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The Aryl hydrocarbon receptor (AhR) is member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones.
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Identifiers
Symbol ARNTL2

Entrez 56938
HUGO 18984

RefSeq NM_020183
UniProt Q8WYA4
Other data

Locus Chr. 12 p12.2-11.2 Bmal (brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like
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Circadian Locomotor Output Cycles Kaput, or Clock is a gene which encodes proteins regulating circadian rhythm. The CLOCK protein seems to affect both the persistence and length of the circadian cycle. CLOCK forms part of a basic-helix-loop-helix transcription factor.
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E2F is a group of genes that codifies a family of transcription factors (TF) in higher eukaryotes. Three of them are activators: E2F1,2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8.
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Identifiers
Symbol HIF3A

Entrez 64344
HUGO 15825
OMIM 609976

RefSeq NM_152794
UniProt Q9Y2N7
Other data

Locus Chr. 19 q13 Hypoxia inducible factors (HIFs)
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Myc (cMyc) is a protooncogene, which is overexpressed in a wide range of human cancers. When it is specifically-mutated, or overexpressed, it increases cell proliferation and functions as an oncogene.
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