promegestone

Summary

Summary: A synthetic progestin which is useful for the study of progestin distribution and progestin tissue receptors, as it is not bound by transcortin and binds to progesterone receptors with a higher association constant than progesterone.

Top Publications

  1. Rayasam G, Elbi C, Walker D, Wolford R, Fletcher T, Edwards D, et al. Ligand-specific dynamics of the progesterone receptor in living cells and during chromatin remodeling in vitro. Mol Cell Biol. 2005;25:2406-18 pubmed
  2. Vicent G, Nacht A, Font Mateu J, Castellano G, Gaveglia L, Ballaré C, et al. Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation. Genes Dev. 2011;25:845-62 pubmed publisher
    ..Chromatin immunoprecipitation (ChIP) and sequencing (ChIP-seq) and expression arrays show that H1 displacement is required for hormone induction of most hormone target genes, some of which are involved in cell proliferation. ..
  3. Treviño L, Bolt M, Grimm S, Edwards D, Mancini M, Weigel N. Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK. Mol Endocrinol. 2016;30:158-72 pubmed publisher
    ..Taken together, these results indicate that the 2 kinases regulate PR transcriptional activity by distinct mechanisms. ..
  4. Grubb G, Spielmann D, Pickar J, Constantine G. Clinical experience with trimegestone as a new progestin in HRT. Steroids. 2003;68:921-6 pubmed
    ..Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis. ..
  5. Pasapera A, Gutierrez Sagal R, García Becerra R, Ulloa Aguirre A, Savouret J. Transactivation of progestin- and estrogen-responsive promoters by 19-nor progestins in African Green Monkey Kidney CV1 cells. Endocrine. 2001;16:217-25 pubmed
    ..In the particular case of NET, the assay system allowed us to determine that the single or multiple hormonal transcriptional effects of this compound are partially mediated by its A-ring-reduced derivatives. ..
  6. Giangrande P, Kimbrel E, Edwards D, McDonnell D. The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding. Mol Cell Biol. 2000;20:3102-15 pubmed
    ..Furthermore, our experiments indicate that hPRA interacts efficiently with the corepressor SMRT and that this activity permits it to function as a transdominant repressor. ..
  7. Wade H, Kobayashi S, Eaton M, Jansen M, Lobenhofer E, Lupien M, et al. Multimodal regulation of E2F1 gene expression by progestins. Mol Cell Biol. 2010;30:1866-77 pubmed publisher
    ..Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR. ..
  8. Bychowski M, Auger C. Progesterone impairs social recognition in male rats. Horm Behav. 2012;61:598-604 pubmed publisher
    ..These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. ..
  9. Smid Koopman E, Blok L, Kuhne L, Burger C, Helmerhorst T, Brinkmann A, et al. Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig. 2003;10:49-57 pubmed
    ..Moreover, antiproliferative actions of progesterone on human endometrial cancer cells could be observed only in the PRB-expressing cell line. ..

More Information

Publications62

  1. Peluffo M, Young K, Stouffer R. Dynamic expression of caspase-2, -3, -8, and -9 proteins and enzyme activity, but not messenger ribonucleic acid, in the monkey corpus luteum during the menstrual cycle. J Clin Endocrinol Metab. 2005;90:2327-35 pubmed
    ..The increased caspase activity at mid-late stage suggests that apoptosis is involved in early luteolysis in primates. Gonadotropin, perhaps via local steroids, modulates initiator caspases in the primate CL. ..
  2. Pant A, Lee I, Lu Z, Rueda B, Schink J, Kim J. Inhibition of AKT with the orally active allosteric AKT inhibitor, MK-2206, sensitizes endometrial cancer cells to progestin. PLoS ONE. 2012;7:e41593 pubmed publisher
    ..In summary, inhibition of AKT stabilizes the Progesterone Receptor B and augments progesterone response in endometrial cancer cells that have hyperactivated AKT. ..
  3. Edwards H, Epps T, Carlen P, J MacLusky N. Progestin receptors mediate progesterone suppression of epileptiform activity in tetanized hippocampal slices in vitro. Neuroscience. 2000;101:895-906 pubmed
    ..After tetanization, however, progesterone receptor-mediated responses become quantitatively more important as a mechanism for suppressing hippocampal electrical activity. ..
  4. Fanjul L, Estevez F, Déniz Cáceres A, Marrero I, Benitez L, Centol I, et al. The androgen receptor does not mediate progestin regulation of progesterone biosynthesis in cultured rat granulosa cells. Biochem Int. 1989;19:977-84 pubmed
  5. Silva B, Martinez D, Wender M. A randomized, controlled pilot trial of hormone therapy for menopausal insomnia. Arch Womens Ment Health. 2011;14:505-8 pubmed publisher
    ..Sleep efficiency and median score of the PSQI improved significantly in the hormone therapy group (HT) (p=0.041 and p=0.027, respectively) and not in placebo group. Perimenopausal insomnia improved after short-term HT. ..
  6. Clemm D, Sherman L, Boonyaratanakornkit V, Schrader W, Weigel N, Edwards D. Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody. Mol Endocrinol. 2000;14:52-65 pubmed
    ..That Ser 294 lies within an inhibitory domain that mediates the unique repressive functions of PR-A raises the possibility that differential phosphorylation of Ser 294 is involved in the distinct functional properties of PR-A and PR-B. ..
  7. Narayanan R, Edwards D, Weigel N. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005;25:2885-98 pubmed
  8. Li H, Yao Z, Degenhardt B, Teper G, Papadopoulos V. Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide. Proc Natl Acad Sci U S A. 2001;98:1267-72 pubmed
    ..We examined (i) the PBR-cholesterol interaction by UV crosslinking of the C17 side-chain containing progestin, promegestone, and (ii) the role of the CRAC domain of PBR in Leydig cell steroidogenesis by using a transducible peptide ..
  9. Haslam S, Drolet A, Smith K, Tan M, Aupperlee M. Progestin-regulated luminal cell and myoepithelial cell-specific responses in mammary organoid culture. Endocrinology. 2008;149:2098-107 pubmed publisher
    ..These results led us to conclude that RANKL, induced by progestin in PR-positive cells, is secreted and interacts with HGF to specifically increase proliferation of PR-negative MECs. ..
  10. Zhang D, Zhang X, Michel F, Blum J, Simmen F, Simmen R. Direct interaction of the Krüppel-like family (KLF) member, BTEB1, and PR mediates progesterone-responsive gene expression in endometrial epithelial cells. Endocrinology. 2002;143:62-73 pubmed
  11. Meuwissen J, Beijers De Bie L, Vihtamaki T, Tuimala R, Siseles N, Magaril C, et al. Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone. Gynecol Endocrinol. 2002;16:155-62 pubmed
    ..The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile. ..
  12. Fernandez H, Lucas C, Hedon B, Meyer J, Mayenga J, Roux C. One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial. Hum Reprod. 2004;19:1465-71 pubmed
    ..A norprogesterone derivative, promegestone, was assessed for the first time in a double-blind trial...
  13. Post M, Rosing J, van der Mooren M, Zweegman S, van Baal W, Kenemans P, et al. Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. Br J Haematol. 2002;119:1017-23 pubmed
    ..In contrast, hormone replacement therapy had no effect on FVIII:Ag. Oral E2 and E2 + D had a small, favourable effect on FXI:Ag. ..
  14. Molina Molina J, Hillenweck A, Jouanin I, Zalko D, Cravedi J, Fernandez M, et al. Steroid receptor profiling of vinclozolin and its primary metabolites. Toxicol Appl Pharmacol. 2006;216:44-54 pubmed
  15. Seeger H, Wallwiener D, Mueck A. Effects of drospirenone on cardiovascular markers in human aortic endothelial cells. Climacteric. 2009;12:80-7 pubmed publisher
    ..absence of aldosterone and compared to progesterone and the progestogens medroxyprogesterone acetate (MPA) and promegestone (R5020), and the antimineralocorticoid spironolactone...
  16. Warming L, Ravn P, Spielman D, Delmas P, Christiansen C. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women. Menopause. 2004;11:337-42 pubmed
    ..Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term. ..
  17. Kariagina A, Xie J, Langohr I, Opreanu R, Basson M, Haslam S. Progesterone decreases levels of the adhesion protein E-cadherin and promotes invasiveness of steroid receptor positive breast cancers. Horm Cancer. 2013;4:371-80 pubmed publisher
    ..These results suggest that progesterone signaling via PRB contributes to tumor invasiveness and can provide an important therapeutic target for treatment of invasive ER+PR+ breast cancers. ..
  18. Young K, Stouffer R. Gonadotropin and steroid regulation of matrix metalloproteinases and their endogenous tissue inhibitors in the developed corpus luteum of the rhesus monkey during the menstrual cycle. Biol Reprod. 2004;70:244-52 pubmed
    ..In contrast, LH promotes TIMP expression, perhaps via steroids, including P. ..
  19. Hubler T, Denny W, Valentine D, Cheung Flynn J, Smith D, Scammell J. The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness. Endocrinology. 2003;144:2380-7 pubmed
    ..Furthermore, overexpression of FKBP51 in the squirrel monkey may be a contributing cause of progesterone resistance in this species. ..
  20. Malet C, Vacca A, Kuttenn F, Mauvais Jarvis P. 17 beta-estradiol dehydrogenase (E2DH) activity in T47D cells. J Steroid Biochem Mol Biol. 1991;39:769-75 pubmed
    ..This observation underlines the possible interest of E2DH assay in parallel to estradiol receptor and PR to evaluate hormone-dependence of breast cancer. ..
  21. Onate S, Tsai S, Tsai M, O Malley B. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995;270:1354-7 pubmed
    ..Together, these results indicate that SRC-1 encodes a coactivator that is required for full transcriptional activity of the steroid receptor superfamily. ..
  22. Le Bihan S, Marsaud V, Mercier Bodard C, Baulieu E, Mader S, White J, et al. Calcium/calmodulin kinase inhibitors and immunosuppressant macrolides rapamycin and FK506 inhibit progestin- and glucocorticosteroid receptor-mediated transcription in human breast cancer T47D cells. Mol Endocrinol. 1998;12:986-1001 pubmed
    ..These observations support the concept that FKBP51 and FKBP52 can act as regulators of Rap and FK506 activity upon PR and GR-mediated transcription, a mechanism that could be also regulated by type II and/or type IV CaMKs. ..
  23. Yang S, Fang Z, Gurates B, Tamura M, Miller J, Ferrer K, et al. Stromal PRs mediate induction of 17beta-hydroxysteroid dehydrogenase type 2 expression in human endometrial epithelium: a paracrine mechanism for inactivation of E2. Mol Endocrinol. 2001;15:2093-105 pubmed
  24. Mueller M, Vigne J, Pritts E, Chao V, Dreher E, Taylor R. Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells. Fertil Steril. 2003;79:386-92 pubmed
    ..However, hPR-mediated transcriptional regulation of the VEGF promoter is complex and cannot be localized to confined PRE sequences. Other response element motifs are likely to play a contributory role. ..
  25. Qiu M, Olsen A, Faivre E, Horwitz K, Lange C. Mitogen-activated protein kinase regulates nuclear association of human progesterone receptors. Mol Endocrinol. 2003;17:628-42 pubmed
    ..These results support a regulatory role for MAPK in nuclear steroid hormone receptor subcellular localization and coupling to multiple PR functions. ..
  26. Winneker R, Bitran D, Zhang Z. The preclinical biology of a new potent and selective progestin: trimegestone. Steroids. 2003;68:915-20 pubmed
    ..The results indicate that TMG is a potent and selective progestin with a preclinical profile well suited for hormone replacement therapy. ..
  27. Bertucci P, Nacht A, Allo M, Rocha Viegas L, Ballaré C, Soronellas D, et al. Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation. Nucleic Acids Res. 2013;41:6072-86 pubmed publisher
    ..These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes. ..
  28. Al Azzawi F, Wahab M, Sami S, Proudler A, Thompson J, Stevenson J. Randomized trial of effects of estradiol in combination with either norethisterone acetate or trimegestone on lipids and lipoproteins in postmenopausal women. Climacteric. 2004;7:292-300 pubmed
    ..Overall, the results of this study suggest that the use of trimegestone in combination with estradiol may be preferable to norethisterone acetate because of the more favorable HDL and apo AI profile. ..
  29. Perry G, Welshons W, Bott R, Smith M. Basis of melengestrol acetate action as a progestin. Domest Anim Endocrinol. 2005;28:147-61 pubmed
  30. Sillem M, Prifti S, Koch A, Neher M, Jauckus J, Runnebaum B. Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis. Eur J Obstet Gynecol Reprod Biol. 2001;95:167-74 pubmed
    ..cells from 19 regularly cycling women with and 32 without endometriosis were treated with diethyl stilbestrol, promegestone (R5020), interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha)...
  31. Telleria C, Stocco C, Stati A, Deis R. Progesterone receptor is not required for progesterone action in the rat corpus luteum of pregnancy. Steroids. 1999;64:760-6 pubmed
    ..a second functional study, luteal cells obtained from 19-day pregnant rats responded to the synthetic progestin promegestone (R5020) in a dose-dependent manner, with an increase in the progesterone output...
  32. Lu Y, Liao Q, Chen C, Yu L. [Functional study of progesterone receptor isoforms in endometrial cancer cell lines]. Beijing Da Xue Xue Bao Yi Xue Ban. 2006;38:475-9 pubmed
    ..Progestin (R5020) inhibits the hyperplasia induced by E2,PR-B is involved in the inhibitory effect of R5020. RU486 antagonizes the effect of R5020,inhibiting cell growth, PR-B is involved in the antagonizing effect of RU486. ..
  33. Conkright M, Asem E. Intracrine role of progesterone in follicle-stimulating hormone- and cyclic adenosine 3',5'-monophosphate-induced fibronectin production and deposition by chicken granulosa cells: influence of follicular development. Endocrinology. 1995;136:2641-51 pubmed
  34. Sriraman V, Sinha M, Richards J. Progesterone receptor-induced gene expression in primary mouse granulosa cell cultures. Biol Reprod. 2010;82:402-12 pubmed publisher
    ..Because Edn1, Apoa1, and Cited1 are known to regulate angiogenesis, PGR may affect the neovascularization of follicles that is initiated with ovulation. ..
  35. Shatnawi A, Tran T, Ratnam M. R5020 and RU486 act as progesterone receptor agonists to enhance Sp1/Sp4-dependent gene transcription by an indirect mechanism. Mol Endocrinol. 2007;21:635-50 pubmed
  36. Vallejo G, Ballaré C, Barañao J, Beato M, Saragueta P. Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells. Mol Endocrinol. 2005;19:3023-37 pubmed
  37. Jacobsen B, Richer J, Schittone S, Horwitz K. New human breast cancer cells to study progesterone receptor isoform ratio effects and ligand-independent gene regulation. J Biol Chem. 2002;277:27793-800 pubmed
    ..Finally, we have described several genes that are regulated by induced PR-A even in the absence of ligand. ..
  38. Gaspard U. [Pharma-Clinics. Medication of the month. Totelle Cycle: new sequential estrogen/progesterone regimen for hormone replacement therapy in menopause]. Rev Med Liege. 2002;57:408-12 pubmed
    ..This particular profile confers to trimegestone its metabolic neutrality and concurs to the high degree of safety and tolerance observed in studies related to Totelle Cycle. ..
  39. Jondet M, Dehennin L. Impact of different progestins on endometrial vascularisation of postmenopausal women. A retrospective image analysis-morphometric study. Maturitas. 2003;46:165-71 pubmed
    ..Twelve women received intranasal estradiol, 300 microg/day from days 1 to 25 combined with 0.5 mg of promegestone from days 11 to 24...
  40. Fitzpatrick S, Berrodin T, Jenkins S, Sindoni D, Deecher D, Frail D. Effect of estrogen agonists and antagonists on induction of progesterone receptor in a rat hypothalamic cell line. Endocrinology. 1999;140:3928-37 pubmed
  41. Gambacciani M, Spielmann D, Genazzani A. Efficacy on climacteric symptoms of a continuous combined regimen of 1 mg 17beta-estradiol and trimegestone versus two regimens combining 1 or 2 mg 17beta-estradiol and norethisterone acetate. Gynecol Endocrinol. 2005;21:65-73 pubmed
    ..Furthermore, trimegestone appeared to provide a better improvement of depressive mood than 0.5 mg NETA when combined with 1 mg 17beta-estradiol. ..
  42. Su E, Cheng Y, Chatterton R, Lin Z, Yin P, Reierstad S, et al. Regulation of 17-beta hydroxysteroid dehydrogenase type 2 in human placental endothelial cells. Biol Reprod. 2007;77:517-25 pubmed
    ..Together, these data indicate that regulation of HSD17B2 mRNA levels and enzymatic activity by RA in the placenta is mediated by RARA and RXRA. ..
  43. Faivre E, Daniel A, Hillard C, Lange C. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008;22:823-37 pubmed publisher
    ..Our data demonstrate the therapeutic potential for PR-targeted breast cancer treatment by exploiting multiple nodes along the PR signaling pathway, including PR-B, EGFR, c-Src, MAPK, or Sp1. ..
  44. Mori T, Murata M, Yoshino T, Nakasono S, Saito F, Takeyama H, et al. A stable human progesterone receptor expressing HeLa reporter cell line as a tool in chemical evaluation at the different cell-cycle phases. Toxicol Lett. 2009;186:123-9 pubmed publisher
    ..hPRLuc-20 cells, they were synchronized to the G(1), S and G(2) phases and treated with progesterone (PROG) and promegestone (R5020)...
  45. Holley A, Kiningham K, Spitz D, Edwards D, Jenkins J, Moore M. Progestin stimulation of manganese superoxide dismutase and invasive properties in T47D human breast cancer cells. J Steroid Biochem Mol Biol. 2009;117:23-30 pubmed publisher
    ..To our knowledge, this is the first characterization of progestin stimulation of MnSOD in human breast cancer cells. ..
  46. Li Y, Kasson B. Androgens augment vasoactive intestinal peptide- and growth hormone-releasing hormone-stimulated progestin production by rat granulosa cells. Endocrinology. 1993;132:584-90 pubmed
    ..These studies demonstrate that androgens, but not estrogens, progestins, or glucocorticoids, augment VIP- and GH-releasing hormone-stimulated progestin production by cultured rat granulosa cells. ..
  47. Thomas M, Bader C, Monet J. Sex steroid hormone modulation of NADPH pathways in MCF-7 cells. Cancer Res. 1990;50:1195-200 pubmed
    ..Our results show that G6PD is increased by 17 beta-estradiol (estradiol) and synthetic progestin (promegestone R5020). The synthetic antiestrogen tamoxifen has no effect on G6PD activity...
  48. Uzan S, Denis C, Pomi V, Varin C. Double-blind trial of promegestone (R 5020) and lynestrenol in the treatment of benign breast disease. Eur J Obstet Gynecol Reprod Biol. 1992;43:219-27 pubmed
    ..thirty-two women between the ages of 19 and 50, with various forms of benign breast diseases received 1 mg promegestone, or 0.5 mg promegestone, or 10 mg lynestrenol daily (double-blind), for 15 days per cycle, during three cycles...
  49. Cann J, Coombs R, Howlett G, Jacobsen M, Winzor D. Effects of molecular crowding on protein self-association: a potential source of error in sedimentation coefficients obtained by zonal ultracentrifugation in a sucrose gradient. Biochemistry. 1994;33:10185-90 pubmed
    ..These features are illustrated by the results of computer-simulated sedimentation of reversibly dimerizing systems in a sucrose gradient, and by conventional sedimentation velocity experiments on yeast enolase. ..
  50. Nordeen S, Ogden C, Taraseviciene L, Lieberman B. Extreme position dependence of a canonical hormone response element. Mol Endocrinol. 1998;12:891-8 pubmed
    ..This may be indicative of cell type-specific interactions between steroid receptors and adapter/coactivator proteins or cell type-specific activities such as acetylases or deacetylases participating in the steroid response. ..
  51. Al Azzawi F, Wahab M, Thompson J, Pornel B, Hirvonen E, Ylikorkala O, et al. Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate. Climacteric. 2001;4:343-54 pubmed
    ..25 mg or E2 + NETA group. All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern. ..
  52. Fanjul L, Gonzalez J, Santana P, Estevez F, Quintana J, Ruiz de Galarreta C. R5020 enhances PGE2 stimulated steroidogenesis in cultured rat granulosa cells. Rev Esp Fisiol. 1992;48:167-70 pubmed
    ..These findings may represent another example of an autocrine control mechanism in which the steroidogenic product of the granulosa cell exerts an ultra-short loop regulation of its own production. ..
  53. Schwarzenbach H, Manna P, Stocco D, Chakrabarti G, Mukhopadhyay A. Stimulatory effect of progesterone on the expression of steroidogenic acute regulatory protein in MA-10 Leydig cells. Biol Reprod. 2003;68:1054-63 pubmed
    ..Furthermore, these results provide a new insight, indicating that progesterone mediates the activation of StAR expression exerted presumably through a novel, nonclassical progesterone receptor in mouse Leydig cells. ..