• 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]
Contents
1Function
2Structure
3Isoforms
4Functional polymorphisms
5Biological role
6Ligands
6.1Agonists
6.2Mixed
6.3Antagonists
7Interactions
8See also
9References
10Further reading
11External links
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
Progesterone receptor, N-terminal
Identifiers
Symbol
Progest_rcpt_N
Pfam
PF02161
InterPro
IPR000128
Available protein structures:
Pfam
structures
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
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
Main articles: Progesterone receptor A, Progesterone receptor B, and Progesterone receptor C
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]
^Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E (March 1987). "Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA". Biochemical and Biophysical Research Communications. 143 (2): 740–8. doi:10.1016/0006-291X(87)91416-1. PMID 3551956.
^Law ML, Kao FT, Wei Q, Hartz JA, Greene GL, Zarucki-Schulz T, Conneely OM, Jones C, Puck TT, O'Malley BW (May 1987). "The progesterone receptor gene maps to human chromosome band 11q13, the site of the mammary oncogene int-2". Proceedings of the National Academy of Sciences of the United States of America. 84 (9): 2877–81. doi:10.1073/pnas.84.9.2877. PMC 304763. PMID 3472240.
^ensembl.org, Gene: ESR1 (ENSG00000091831)
^Gadkar-Sable S, Shah C, Rosario G, Sachdeva G, Puri C (2005). "Progesterone receptors: various forms and functions in reproductive tissues". Frontiers in Bioscience. 10: 2118–30. doi:10.2741/1685. PMID 15970482.
^Kase NG, Speroff L, Glass RL (1999). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-683-30379-1.
^Fritz MA, Speroff L (2005). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-4795-3.
^Tommaso Falcone; William W. Hurd (22 May 2013). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. pp. 39–. ISBN 978-1-4614-6837-0.
^Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (May 1990). "Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B". The EMBO Journal. 9 (5): 1603–14. PMC 551856. PMID 2328727.
^Terry KL, De Vivo I, Titus-Ernstoff L, Sluss PM, Cramer DW (March 2005). "Genetic variation in the progesterone receptor gene and ovarian cancer risk". American Journal of Epidemiology. 161 (5): 442–51. doi:10.1093/aje/kwi064. PMC 1380205. PMID 15718480.
^De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, Hunter DJ (September 2002). "A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk". Proceedings of the National Academy of Sciences of the United States of America. 99 (19): 12263–8. doi:10.1073/pnas.192172299. PMC 129433. PMID 12218173.
^Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (June 2004). "No association between the progesterone receptor gene +331G/A polymorphism and breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 13 (6): 1084–5. PMID 15184270.
^Dossus L, Canzian F, Kaaks R, Boumertit A, Weiderpass E (July 2006). "No association between progesterone receptor gene +331G/A polymorphism and endometrial cancer". Cancer Epidemiology, Biomarkers & Prevention. 15 (7): 1415–6. doi:10.1158/1055-9965.EPI-06-0215. PMID 16835347.
^Hilton HN, Graham JD, Clarke CL (September 2015). "Minireview: Progesterone Regulation of Proliferation in the Normal Human Breast and in Breast Cancer: A Tale of Two Scenarios?". Molecular Endocrinology. 29 (9): 1230–42. doi:10.1210/me.2015-1152. PMID 26266959.
^Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ (2013). "Amphiregulin mediates progesterone-induced mammary ductal development during puberty". Breast Cancer Research. 15 (3): R44. doi:10.1186/bcr3431. PMC 3738150. PMID 23705924.
^ abKnutson TP, Lange CA (April 2014). "Tracking progesterone receptor-mediated actions in breast cancer". Pharmacology & Therapeutics. 142 (1): 114–25. doi:10.1016/j.pharmthera.2013.11.010. PMC 3943696. PMID 24291072.
^Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC (June 2003). "Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells". The Journal of Biological Chemistry. 278 (24): 21474–82. doi:10.1074/jbc.M212098200. PMID 12672823.
^Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP (May 2000). "The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding". Molecular and Cellular Biology. 20 (9): 3102–15. doi:10.1128/MCB.20.9.3102-3115.2000. PMC 85605. PMID 10757795.
^Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (February 1999). "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily". Molecular and Cellular Biology. 19 (2): 1182–9. doi:10.1128/mcb.19.2.1182. PMC 116047. PMID 9891052.
Conneely OM, Mulac-Jericevic B, Lydon JP (November 2003). "Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms". Steroids. 68 (10–13): 771–8. doi:10.1016/S0039-128X(03)00126-0. PMID 14667967.
Bagchi MK, Tsai SY, Tsai MJ, O'Malley BW (April 1992). "Ligand and DNA-dependent phosphorylation of human progesterone receptor in vitro". Proceedings of the National Academy of Sciences of the United States of America. 89 (7): 2664–8. doi:10.1073/pnas.89.7.2664. PMC 48722. PMID 1557371.
Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (May 1990). "Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B". The EMBO Journal. 9 (5): 1603–14. PMC 551856. PMID 2328727.
Guiochon-Mantel A, Loosfelt H, Lescop P, Sar S, Atger M, Perrot-Applanat M, Milgrom E (June 1989). "Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers". Cell. 57 (7): 1147–54. doi:10.1016/0092-8674(89)90052-4. PMID 2736623.
Fernandez MD, Carter GD, Palmer TN (January 1983). "The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol". British Journal of Clinical Pharmacology. 15 (1): 95–101. doi:10.1111/j.1365-2125.1983.tb01470.x. PMC 1427833. PMID 6849751.
Oñate SA, Tsai SY, Tsai MJ, O'Malley BW (November 1995). "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science. 270 (5240): 1354–7. doi:10.1126/science.270.5240.1354. PMID 7481822.
Zhang Y, Beck CA, Poletti A, Edwards DP, Weigel NL (December 1994). "Identification of phosphorylation sites unique to the B form of human progesterone receptor. In vitro phosphorylation by casein kinase II". The Journal of Biological Chemistry. 269 (49): 31034–40. PMID 7983041.
Mansour I, Reznikoff-Etievant MF, Netter A (August 1994). "No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy". Human Reproduction. 9 (8): 1546–9. doi:10.1093/oxfordjournals.humrep.a138746. PMID 7989520.
Kalkhoven E, Wissink S, van der Saag PT, van der Burg B (March 1996). "Negative interaction between the RelA(p65) subunit of NF-kappaB and the progesterone receptor". The Journal of Biological Chemistry. 271 (11): 6217–24. doi:10.1074/jbc.271.11.6217. PMID 8626413.
Wang JD, Zhu JB, Fu Y, Shi WL, Qiao GM, Wang YQ, Chen J, Zhu PD (February 1996). "Progesterone receptor immunoreactivity at the maternofetal interface of first trimester pregnancy: a study of the trophoblast population". Human Reproduction. 11 (2): 413–9. doi:10.1093/humrep/11.2.413. PMID 8671234.
Thénot S, Henriquet C, Rochefort H, Cavaillès V (May 1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". The Journal of Biological Chemistry. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.
Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, O'Malley BW (July 1997). "Steroid receptor induction of gene transcription: a two-step model". Proceedings of the National Academy of Sciences of the United States of America. 94 (15): 7879–84. doi:10.1073/pnas.94.15.7879. PMC 21523. PMID 9223281.
Shanker YG, Sharma SC, Rao AJ (September 1997). "Expression of progesterone receptor mRNA in the first trimester human placenta". Biochemistry and Molecular Biology International. 42 (6): 1235–40. doi:10.1080/15216549700203701. PMID 9305541.
Richer JK, Lange CA, Wierman AM, Brooks KM, Tung L, Takimoto GS, Horwitz KB (April 1998). "Progesterone receptor variants found in breast cells repress transcription by wild-type receptors". Breast Cancer Research and Treatment. 48 (3): 231–41. doi:10.1023/A:1005941117247. PMID 9598870.
Williams SP, Sigler PB (May 1998). "Atomic structure of progesterone complexed with its receptor". Nature. 393 (6683): 392–6. doi:10.1038/30775. PMID 9620806.
Boonyaratanakornkit V, Melvin V, Prendergast P, Altmann M, Ronfani L, Bianchi ME, Taraseviciene L, Nordeen SK, Allegretto EA, Edwards DP (August 1998). "High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells". Molecular and Cellular Biology. 18 (8): 4471–87. doi:10.1128/mcb.18.8.4471. PMC 109033. PMID 9671457.
Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (February 1999). "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily". Molecular and Cellular Biology. 19 (2): 1182–9. doi:10.1128/mcb.19.2.1182. PMC 116047. PMID 9891052.
External links
Progesterone+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
v
t
e
PDB gallery
1a28: HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN
1e3k: HUMAN PROGESTERON RECEPTOR LIGAND BINDING DOMAIN IN COMPLEX WITH THE LIGAND METRIBOLONE (R1881)
1sqn: Progesterone Receptor Ligand Binding Domain with bound Norethindrone
1sr7: Progesterone Receptor Hormone Binding Domain with Bound Mometasone Furoate
1zuc: Progesterone receptor ligand binding domain in complex with the nonsteroidal agonist tanaproget
2c7a: STRUCTURE OF THE PROGESTERONE RECEPTOR-DNA COMPLEX
2ovh: Progesterone Receptor with Bound Asoprisnil and a Peptide from the Co-Repressor SMRT
2ovm: Progesterone Receptor with Bound Asoprisnil and a Peptide from the Co-Repressor NCoR
7
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Main article: Taifa of Zaragoza Al-Mu'taman Ruler of Zaragoza Reign 1081–1085 Predecessor Ahmad al-Muqtadir Successor Al-Mustain II Born Zaragoza Died 1085 Full name Yusuf ibn Ahmad al-Mu'taman ibn Hūd House Banu Hud Yusuf ibn Ahmad al-Mu'taman ibn Hūd (Arabic: المؤتمن بالله يوسف إبن أحمد إبن هود , al-Mutaman bi l-Lah , died c. 1085) was the third king of the Banu Hud dynasty who ruled over the Taifa of Zaragoza from 1081 to 1085. Yusuf al-Mutaman reigned during the height of power of Muslim Zaragoza , following the thriving period of his father Ahmad al-Muqtadir. He continued his father's efforts and created around him a court of intellectuals, living in the beautiful palace of Aljafería, nicknamed as "the palace of joy". Al-Mu'taman was also a scholarly king and a patron of science, philosophy and arts. As an example of a wise king, he knew astrology, philosophy, and especially mathematics, a discipline in which
This article is about the vegetable. For other uses, see Zucchini (disambiguation). Zucchini (courgette) A striped and a uniform color zucchini Genus Cucurbita Species Cucurbita pepo Origin 19th century northern Italy The zucchini ( / z uː ˈ k iː n i / , American English) or courgette ( / k ʊər ˈ ʒ ɛ t / , British English) is a summer squash which can reach nearly 1 metre (100 cm; 39 in) in length, but is usually harvested when still immature at about 15 to 25 cm (6 to 10 in). [1] A zucchini is a thin-skinned cultivar of what in Britain and Ireland is referred to as a marrow. [2] [3] In South Africa, a zucchini is known as a baby marrow. Along with certain other squashes and pumpkins, the zucchini belongs to the species Cucurbita pepo . It can be dark or light green. A related hybrid, the golden zucchini, is a deep yellow or orange color. [4] In a culinary context, the zucchini is treated as a vegetable; it is usually cooked and presented as a savory dish o
