In vitro characterization of trimegestone: a new potent and selective progestin

摘要: Trimegestone (TMG) is a novel 19-norpregnane progestin under development for hormone replacement therapy and oral contraception. The objective of the current study was to characterize potency steroid receptor selectivity TMG in several vitro assays compare its activity that medroxyprogesterone acetate (MPA). MPA had similar competitive binding affinity human rabbit progesterone (PR). However, significantly higher rat PR (IC(50) = 3.3 nM) than 53.3 nM). In T47D cells, both compounds increased alkaline phosphatase cell proliferation with comparable potencies (EC(50s) 0.1 nM 0.02 nM, respectively). To further progestational selectivity, we established an immortalized endometrial stromal line (HESC-T). This lacks endogenous estrogen (ER) but does have functional glucocorticoid receptors (GR). When ER transiently expressed 17beta-estradiol (E(2)) induces PR, allowing PR-regulated genes. HESC-T cells expressing exogenous ER, therefore HRE-tk-luciferase tenfold EC(50) 0.2 nM. without no did not induce activity, whereas induced reporter about 10 MPA-induced believed be mediated through GR. evaluated using assay lung carcinoma A549, which contains GR PR. these effect on luciferase dose-dependent manner approximately 30 Furthermore, mouse fibroblast L929, expresses androgen (AR) showed weak antiandrogenic androgenic activity. summary, data from demonstrate potent better profile MPA.