Progesteronski receptor

Progesteronski receptor, N-kraj
Progesteronski receptor, N-kraj
Identifikatori
Simbol	Progest_rcpt_N

Progesteronski receptor
Progesteronski receptor
Identifikatori
Simbol	PGR
Alt. simboli	NR3C3; PR Raspon ekspresije gena PGR
NCBI gen	5241
HGNC	8910
OMIM	607311
PDB	1A28 1E3K, 1SQN, 1SR7, 1ZUC, 2C7A, 2OVH, 2OVM, 2W8Y, 3D90, 3G8N, 3G8O, 3HQ5, 3KBA

Progesteronski receptor (PR), poznat kao NR3C3 ili potporodica 3 jedarnih receptora, grupa C, čjan 3, je protein koji se nalazi unutar ćelija. Aktivira ga steroidni hormon progesteron.

Kod ljudi, PR je kodiran jednim PGR genom koji se nalazi na dugom kraku hromosoma11, pozicija 11q22 ,^[1]^[2]^[3] ima dvije izoforme, PR-A i PR-B, koje se razlikuju u molekulskoj težini.^[4]^[5]^[6] PR-B je pozitivni regulator efekata progesterona, dok PR-A služi za antagonizaciju efekata PR-B.^[7]

Mehanizam uredi

Progesteron je neophodan za indukciju receptora progesterona. Kada nema hormona vezanja, karboksilni kraj inhibira transkripciju. Vezanje za hormon inducira strukturne promjene koje uklanjaju inhibitorno djelovanje. Antagonisti progesterona sprečavaju strukturnu rekonfiguraciju.

Nakon što se progesteron veže za receptor, slijedi restrukturiranje sa dimerom i kompleks ulazi u jedro i veže se za DNK. Tamo se odvija transkripcija, što rezultira stvaranjem iRNK koja se i ribosomima prevodi kako bi proizvela određene proteine.

Struktura uredi

Zajedno sa ostalim steroidnim receptorima, progesteronski receptor ima N-krajev regulacijski domen, DNK-vezujući domen, zglobni kompartment i C-krajev domen vezanja liganda. Posebna funkcija aktivacije transkripcije (TAF), nazvana TAF-3, prisutna je u progesteronskom receptoru-B, u B-uzvodnom segmentu (BUS) na aminokiselinskom kraju. Ovaj segment nije prisutan u receptoru-A.

Izoforme uredi

Kao što se pokazalo kod miševa s nedostatkom progesteronskog receptora, fiziološki efekti progesterona u potpunosti ovise o prisustvu ljudskog progesteronskog receptora (hPR), člana superporodice jedarnih receptora za steroidni receptor. Ljudski gen za jednu kopiju (hPR) koristi odvojene promotore i translacijska polazna mjesta za proizvodnju dvije izoforme, hPR-A i -B, koje su identične, osim dodatnih 165 aminokiselina prisutnih samo na N-kraju hPR-B.^[8] Iako hPR-B dijeli mnoge važne strukturne domene s hPR-A, oni su zapravo dva funkcijski različita faktora transkripcije, koji posreduju vlastite gene za odgovor i fiziološke efekte s malim preklapanjem. Selektivna ablacija PR-A na mišjem modelu, koja je rezultirala ekskluzivnom produkcijom PR-B, neočekivano je otkrila da PR-B doprinosi, a ne inhibira, proliferaciju epitelnih ćelija, kao odgovor samo na estrogen i u prisustvu progesterona i estrogena . Ovi rezultati sugeriraju da je u maternici izolacija PR-A neophodna da bi se suprotstavila proliferaciji izazvanoj estrogenom, kao i proliferaciji koja zavisi od PR-B.

Funkcijski polimorfizmi uredi

U ljudskom PR genu. identificirano je šest varijabilnih mjesta, uključujući četiri polimorfizma i pet uobičajenih haplotipova.^[9] Jedan polimorfizam promotorske regije, + 331G/A, stvara jedinstveno početno mjesto transkripcije. Biohemijski testovi pokazali su da polimorfizam + 331G/A povećava transkripciju gena PR, favorizujući proizvodnju hPR-B u ćelijskoj liniji karcinoma endometrija.^[10]

Nekoliko dosadašnjih studija nije pokazalo povezanost između gena progesteronskog receptora + 331G/A polimorfizama i karcinoma dojke ili endometrija.^[11]^[12] Međutim, ovim studijama nedostajala je veličina uzorka i statistička snaga da bi se donijeli konačni zaključci zbog rijetkosti SNP + 331A. Do sada nije poznato koji su polimorfizmi ovog receptora od značaja za rak. Studija o 21 neevropskoj populaciji identifikovala je dva markera unutar PROGINS haplotipa gena PR kao pozitivne korelacije sa rakom jajnika i dojke..^[13]

Ligandi uredi

Interakcije uredi

Pokazano je da receptor za progesteron interreagira sa:

KLF9,^[15]
korepresorom-2 jedarnog receptore,^[16] i
UBE3A.^[17]

Također pogledajte uredi

Reference uredi

^ Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E (mart 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 (maj 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. Bibcode:1987PNAS...84.2877L. 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 (1–3): 2118–30. doi:10.2741/1685. PMID 15970482.
^ Kase, Nathan G.; Speroff, Leon; Glass, Robert L. (1999). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 978-0-683-30379-7.
^ Fritz, Marc A.; Speroff, Leon (2005). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-4795-0.
^ Falcone, Tommaso; Hurd, William W. (22. 5. 2013). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. str. 39–. ISBN 978-1-4614-6837-0.
^ Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.
^ Terry KL, De Vivo I, Titus-Ernstoff L, Sluss PM, Cramer DW (mart 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 (septembar 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. Bibcode:2002PNAS...9912263D. doi:10.1073/pnas.192172299. PMC 129433. PMID 12218173.
^ Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (juni 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 (juli 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.
^ Rockwell, L. C.; Rowe, E. J.; Arnson, K.; Jackson, F.; Froment, A.; Ndumbe, P.; Seck, B.; Jackson, R.; Lorenz, J. G. (2012). "Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers". American Journal of Human Biology. 24 (1): 42–51. doi:10.1002/ajhb.21233. PMID 22121098.
^ ^a ^b Knutson 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 (juni 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 (maj 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 (februar 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.

Dopunska literatura uredi

Butnor KJ, Burchette JL, Robboy SJ (juli 1999). "Progesterone receptor activity in leiomyomatosis peritonealis disseminata". International Journal of Gynecological Pathology. 18 (3): 259–64. doi:10.1097/00004347-199907000-00012. PMID 12090595.
Leonhardt SA, Boonyaratanakornkit V, Edwards DP (novembar 2003). "Progesterone receptor transcription and non-transcription signaling mechanisms". Steroids. 68 (10–13): 761–70. doi:10.1016/S0039-128X(03)00129-6. PMID 14667966.
Conneely OM, Mulac-Jericevic B, Lydon JP (novembar 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. Bibcode:1992PNAS...89.2664B. 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 (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.
Guiochon-Mantel A, Loosfelt H, Lescop P, Sar S, Atger M, Perrot-Applanat M, Milgrom E (juni 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 (januar 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 (novembar 1995). "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science. 270 (5240): 1354–7. Bibcode:1995Sci...270.1354O. doi:10.1126/science.270.5240.1354. PMID 7481822.
Zhang Y, Beck CA, Poletti A, Edwards DP, Weigel NL (decembar 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 (mart 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 (februar 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 (maj 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 (juli 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. Bibcode:1997PNAS...94.7879J. doi:10.1073/pnas.94.15.7879. PMC 21523. PMID 9223281.
Shanker YG, Sharma SC, Rao AJ (septembar 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 (maj 1998). "Atomic structure of progesterone complexed with its receptor". Nature. 393 (6683): 392–6. Bibcode:1998Natur.393..392W. 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 (februar 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.

Vanjski linkovi uredi

Progesterone Receptors na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Transcripcijski factori Šablon:Progestogenika

Mehanizam uredi

Progesteron je neophodan za indukciju receptora progesterona. Kada nema hormona vezanja, karboksilni kraj inhibira transkripciju. Vezanje za hormon inducira strukturne promjene koje uklanjaju inhibitorno djelovanje. Antagonisti progesterona sprečavaju strukturnu rekonfiguraciju.

Nakon što se progesteron veže za receptor, slijedi restrukturiranje sa dimerom i kompleks ulazi u jedro i veže se za DNK. Tamo se odvija transkripcija, što rezultira stvaranjem iRNK koja se i ribosomima prevodi kako bi proizvela određene proteine.

Struktura uredi

Pfam {{{1}}}

Zajedno sa ostalim steroidnim receptorima, progesteronski receptor ima N-krajev regulacijski domen, DNK-vezujući domen, zglobni kompartment i C-krajev domen vezanja liganda. Posebna funkcija aktivacije transkripcije (TAF), nazvana TAF-3, prisutna je u progesteronskom receptoru-B, u B-uzvodnom segmentu (BUS) na aminokiselinskom kraju. Ovaj segment nije prisutan u receptoru-A.

Izoforme uredi

Kao što se pokazalo kod miševa s nedostatkom progesteronskog receptora, fiziološki efekti progesterona u potpunosti ovise o prisustvu ljudskog progesteronskog receptora (hPR), člana superporodice jedarnih receptora za steroidni receptor. Ljudski gen za jednu kopiju (hPR) koristi odvojene promotore i translacijska polazna mjesta za proizvodnju dvije izoforme, hPR-A i -B, koje su identične, osim dodatnih 165 aminokiselina prisutnih samo na N-kraju hPR-B.^[1] Iako hPR-B dijeli mnoge važne strukturne domene s hPR-A, oni su zapravo dva funkcijski različita faktora transkripcije, koji posreduju vlastite gene za odgovor i fiziološke efekte s malim preklapanjem. Selektivna ablacija PR-A na mišjem modelu, koja je rezultirala ekskluzivnom produkcijom PR-B, neočekivano je otkrila da PR-B doprinosi, a ne inhibira, proliferaciju epitelnih ćelija, kao odgovor samo na estrogen i u prisustvu progesterona i estrogena . Ovi rezultati sugeriraju da je u maternici izolacija PR-A neophodna da bi se suprotstavila proliferaciji izazvanoj estrogenom, kao i proliferaciji koja zavisi od PR-B.

Funkcijski polimorfizmi uredi

U ljudskom PR genu. identificirano je šest varijabilnih mjesta, uključujući četiri polimorfizma i pet uobičajenih haplotipova.^[2] Jedan polimorfizam promotorske regije, + 331G/A, stvara jedinstveno početno mjesto transkripcije. Biohemijski testovi pokazali su da polimorfizam + 331G/A povećava transkripciju gena PR, favorizujući proizvodnju hPR-B u ćelijskoj liniji karcinoma endometrija.^[3]

Nekoliko dosadašnjih studija nije pokazalo povezanost između gena progesteronskog receptora + 331G/A polimorfizama i karcinoma dojke ili endometrija.^[4]^[5] Međutim, ovim studijama nedostajala je veličina uzorka i statistička snaga da bi se donijeli konačni zaključci zbog rijetkosti SNP + 331A. Do sada nije poznato koji su polimorfizmi ovog receptora od značaja za rak. Studija o 21 neevropskoj populaciji identifikovala je dva markera unutar PROGINS haplotipa gena PR kao pozitivne korelacije sa rakom jajnika i dojke..^[6]

Ligandi uredi

Agonisti uredi

Endogeni progestogeni (npr., progesteron)
Sintetski progestogeni npr. noretisteron, levonorgestrel, medroksiprogesteron-acetat, megestrol-acetat, didrogesteron, drospirenon)

Mješoviti uredi

Selektivni modulator receptora progesterona (npr. ulipristal-acetat, telapriston-acetat, vilaprisan, asoprisnil, asoprisnil-ekamat)^[7]

Antagonisti uredi

Antiprogestogeni (npr. mifepriston, aglepriston, onapriston, lonaprisan, lilopriston, toripriston)^[7]

Interakcije uredi

Pokazano je da receptor za progesteron interreagira sa:

KLF9,^[8]
korepresorom-2 jedarnog receptore,^[9] i
UBE3A.^[10]

Također pogledajte uredi

Reference uredi

^ Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.
^ Terry KL, De Vivo I, Titus-Ernstoff L, Sluss PM, Cramer DW (mart 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 (septembar 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. Bibcode:2002PNAS...9912263D. doi:10.1073/pnas.192172299. PMC 129433. PMID 12218173.
^ Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (juni 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 (juli 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.
^ Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom ReferenceA
^ ^a ^b Knutson 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 (juni 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 (maj 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 (februar 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.

Dopunska literatura uredi

Butnor KJ, Burchette JL, Robboy SJ (juli 1999). "Progesterone receptor activity in leiomyomatosis peritonealis disseminata". International Journal of Gynecological Pathology. 18 (3): 259–64. doi:10.1097/00004347-199907000-00012. PMID 12090595.
Leonhardt SA, Boonyaratanakornkit V, Edwards DP (novembar 2003). "Progesterone receptor transcription and non-transcription signaling mechanisms". Steroids. 68 (10–13): 761–70. doi:10.1016/S0039-128X(03)00129-6. PMID 14667966.
Conneely OM, Mulac-Jericevic B, Lydon JP (novembar 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. Bibcode:1992PNAS...89.2664B. 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 (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.
Guiochon-Mantel A, Loosfelt H, Lescop P, Sar S, Atger M, Perrot-Applanat M, Milgrom E (juni 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 (januar 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 (novembar 1995). "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science. 270 (5240): 1354–7. Bibcode:1995Sci...270.1354O. doi:10.1126/science.270.5240.1354. PMID 7481822.
Zhang Y, Beck CA, Poletti A, Edwards DP, Weigel NL (decembar 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 (mart 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 (februar 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 (maj 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 (juli 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. Bibcode:1997PNAS...94.7879J. doi:10.1073/pnas.94.15.7879. PMC 21523. PMID 9223281.
Shanker YG, Sharma SC, Rao AJ (septembar 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 (maj 1998). "Atomic structure of progesterone complexed with its receptor". Nature. 393 (6683): 392–6. Bibcode:1998Natur.393..392W. 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 (februar 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.

Vanjski linkovi uredi

Progesterone Receptors na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Transcripcijski factori Šablon:Progestogenika

[pmid3551956-1] Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E (mart 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.

[pmid3472240-2] Law ML, Kao FT, Wei Q, Hartz JA, Greene GL, Zarucki-Schulz T, Conneely OM, Jones C, Puck TT, O'Malley BW (maj 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. Bibcode:1987PNAS...84.2877L. doi:10.1073/pnas.84.9.2877. PMC 304763. PMID 3472240.

[3] sembl.org, Gene: ESR1 (ENSG00000091831)

[pmid15970482-4] 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 (1–3): 2118–30. doi:10.2741/1685. PMID 15970482.

[isbn0-683-30379-1-5] Kase, Nathan G.; Speroff, Leon; Glass, Robert L. (1999). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 978-0-683-30379-7.

[isbn0-7817-4795-3-6] Fritz, Marc A.; Speroff, Leon (2005). Clinical gynecologic endocrinology and infertility. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-4795-0.

[FalconeHurd2013-7] Falcone, Tommaso; Hurd, William W. (22. 5. 2013). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. str. 39–. ISBN 978-1-4614-6837-0.

[pmid2328727-8] Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.

[pmid15718480-9] Terry KL, De Vivo I, Titus-Ernstoff L, Sluss PM, Cramer DW (mart 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.

[pmid12218173-10] De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, Hunter DJ (septembar 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. Bibcode:2002PNAS...9912263D. doi:10.1073/pnas.192172299. PMC 129433. PMID 12218173.

[pmid15184270-11] Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (juni 2004). "No association between the progesterone receptor gene +331G/A polymorphism and breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 13 (6): 1084–5. PMID 15184270.

[pmid16835347-12] Dossus L, Canzian F, Kaaks R, Boumertit A, Weiderpass E (juli 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.

[ReferenceA-13] Rockwell, L. C.; Rowe, E. J.; Arnson, K.; Jackson, F.; Froment, A.; Ndumbe, P.; Seck, B.; Jackson, R.; Lorenz, J. G. (2012). "Worldwide distribution of allelic variation at the progesterone receptor locus and the incidence of female reproductive cancers". American Journal of Human Biology. 24 (1): 42–51. doi:10.1002/ajhb.21233. PMID 22121098.

[pmid24291072-14] Knutson 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.

[pmid12672823-15] Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC (juni 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.

[pmid10757795-16] Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP (maj 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.

[pmid9891052-17] Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (februar 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.

[pmid2328727-18] Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (maj 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. doi:10.1002/j.1460-2075.1990.tb08280.x. PMC 551856. PMID 2328727.

[pmid15718480-19] Terry KL, De Vivo I, Titus-Ernstoff L, Sluss PM, Cramer DW (mart 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.

[pmid12218173-20] De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, Hunter DJ (septembar 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. Bibcode:2002PNAS...9912263D. doi:10.1073/pnas.192172299. PMC 129433. PMID 12218173.

[pmid15184270-21] Feigelson HS, Rodriguez C, Jacobs EJ, Diver WR, Thun MJ, Calle EE (juni 2004). "No association between the progesterone receptor gene +331G/A polymorphism and breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 13 (6): 1084–5. PMID 15184270.

[pmid16835347-22] Dossus L, Canzian F, Kaaks R, Boumertit A, Weiderpass E (juli 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.

[ReferenceA-23] Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom ReferenceA

[pmid24291072-24] Knutson 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.

[pmid12672823-25] Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC (juni 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.

[pmid10757795-26] Giangrande PH, Kimbrel EA, Edwards DP, McDonnell DP (maj 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.

[pmid9891052-27] Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (februar 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]