生物活性

• 描述Progesterone Receptor (PGR) is a member or the steroid receptor superfamily. It mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. Progesterone Receptor is involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The glucocorticoid receptor (GR) has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. The glucocorticoid receptor affects inflammatory responses, cellular proliferation and differentiation in target tissues. The glucocorticoid receptor is involved in chromatin remodeling, plays a role in rapid mRNA degradation. The glucocorticoid receptor could also act as a coactivator for STAT5-dependent transcription upon growth hormone stimulation. Medroxyprogesterone acetate is a progestin, a synthetic variant of the human hormone progesterone. Medroxyprogesterone acetate acts as a ligand that binds to progesterone receptor. Reports also suggested that Medroxyprogesterone acetate also binds the glucocorticoid receptor. The details were that Medroxyprogesterone acetate dose dependently increased α-ENaC promoter-driven luciferase activity in M-1 cells, indicating that Medroxyprogesterone acetate regulates α-ENaC in a progesterone receptor-independent manner. Moreover, when tested in HT29 cells, Medroxyprogesterone acetate could only stimulate α-ENaC-driven reporter activity when glucocorticoid receptor was coexpressed^[3]. According to another report, thyroid cancer KTC-2 cells incubated with 10-1000 nM Medroxyprogesterone acetate for 2 days showed decreased secretion and mRNA expression of IL-6 and PTHrP in a dose-dependent manner. The finding that KTC-2 cells express glucocorticoid receptor but not progesterone receptor suggested that the effect of Medroxyprogesterone acetate was mediated by glucocorticoid receptor^[4]. In a rabbit model of flank wounds, Medroxyprogesterone administrated i.m. at the dose of 35 mg/kg daily prolonged the latent phase of wound healing, slowed the rate and decreased the total amount of contracture^[5]. According to a published study evaluating the mnemonic and neurobiological effects of Medroxyprogesterone acetate in surgically menopausal rats, Medroxyprogesterone acetate was given at the low dose of 14 mg or the high dose of 21 mg via implanted Alzet osmotic pumps, which slowly released the agent in vivo. The results were that both doses of Medroxyprogesterone acetate impaired learning. High dose of Medroxyprogesterone acetate impaired delayed memory retention and exacerbated overnight forgetting. Medroxyprogesterone acetate treatment also significantly decreased GAD levels in the hippocampus and significantly increased GAD levels in the entorhinal cort^[6].

• 动物研究
  剂量	Beagle bitches: 0.2 mg/kg - 75 mg/kg[3] (i.m.) Macaque: 1.5 mg/kg[4] (i.m.)
  给药途径	i.m.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03196492	-	-	Recruiting	June 14, 2019	United States, Maryland ... more >> Johns Hopkins Hospital Recruiting Baltimore, Maryland, United States, 21205 Contact: Okonkwo Collapse <<
  NCT00000897	HIV Infections	Not Applicable	Completed	-	United States, California ... more >> San Francisco AIDS Clinic / San Francisco Gen Hosp San Francisco, California, United States, 941102859 United States, Florida Univ of Florida Health Science Ctr / Pediatrics Jacksonville, Florida, United States, 32209 United States, New York Children's Hosp at Albany Med Ctr Albany, New York, United States, 12208 SUNY / Erie County Med Ctr at Buffalo Buffalo, New York, United States, 14215 United States, North Carolina Univ of North Carolina Chapel Hill, North Carolina, United States, 275997215 United States, Washington Univ of Washington Seattle, Washington, United States, 98104 Collapse <<
  NCT00370019	Premature Ovarian Failure	Phase 2	Withdrawn	-	United States, Maryland ... more >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 Collapse <<

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• 参考文献

• [1] Ciriza I, Carrero P, et al. Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective. J Neurobiol. 2006 Aug;66(9):916-28.

  [2] Kurebayashi J, Otsuki T, et al. Medroxyprogesterone acetate decreases secretion of interleukin-6 and parathyroid hormone-related protein in a new anaplastic thyroid cancer cell line, KTC-2. Thyroid. 2003 Mar;13(3):249-58.

  [3] Thomas CP, Liu KZ, Vats HS. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate alpha-ENaC and sgk1 expression in renal collecting duct epithelia. Am J Physiol Renal Physiol. 2006 Feb;290(2):F306-12. doi: 10.1152/ajprenal.00062.2005. Epub 2005 Sep 27. PMID: 16189295.

  [4] Kurebayashi J, Otsuki T, Tanaka K, Yamamoto Y, Moriya T, Sonoo H. Medroxyprogesterone acetate decreases secretion of interleukin-6 and parathyroid hormone-related protein in a new anaplastic thyroid cancer cell line, KTC-2. Thyroid. 2003 Mar;13(3):249-58. doi: 10.1089/105072503321582042. PMID: 12729473.

  [5] Lenco W, Mcknight M, Macdonald AS. Effects of cortisone acetate, methylprednisolone and medroxyprogesterone on wound contracture and epithelization in rabbits. Ann Surg. 1975 Jan;181(1):67-73. doi: 10.1097/00000658-197501000-00015. PMID: 1119869; PMCID: PMC1343717.

  [6] Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, Scheldrup MR, Bowman BL, Bimonte-Nelson HA. Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem. 2010 Mar;93(3):444-53. doi: 10.1016/j.nlm.2010.01.002. Epub 2010 Jan 13. PMID: 20074654; PMCID: PMC3397202.

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