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 is a progestin, a synthetic variant of the human hormone progesterone. Medroxyprogesterone acts as a ligand that binds to progesterone receptor. Reports also suggested that Medroxyprogesterone also binds the glucocorticoid receptor. The details were that Medroxyprogesterone dose dependently increased α-ENaC promoter-driven luciferase activity in M-1 cells, indicating that Medroxyprogesterone regulates α-ENaC in a progesterone receptor-independent manner. Moreover, when tested in HT29 cells, Medroxyprogesterone could only stimulate α-ENaC-driven reporter activity when glucocorticoid receptor was coexpressed. According to another report, thyroid cancer KTC-2 cells incubated with 10-1000 nM Medroxyprogesterone 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 was mediated by glucocorticoid receptor. 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. According to a published study evaluating the mnemonic and neurobiological effects of Medroxyprogesterone in surgically menopausal rats, Medroxyprogesterone 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 impaired learning. High dose of Medroxyprogesterone impaired delayed memory retention and exacerbated overnight forgetting. Medroxyprogesterone treatment also significantly decreased GAD levels in the hippocampus and significantly increased GAD levels in the entorhinal cort.

• 动物研究
  剂量	Macaque: 0.5 mg/kg - 2.5 mg/kg[2] (i.m.) Cynomolgus monkey: 25 mg/kg - 100 mg/kg[3] (i.m.)
  给药途径	i.m.