A putative stimulatory role of progesterone acting via progesterone receptors in the steroidogenic cells of the human corpus luteum

To further explore the proposed auto-regulatory role of progesterone action in the human corpus luteum (CL), the expression and functional roles of pr ogesterone receptor (PR) isoforms A and B during the luteal phase (LP) of t he menstrual cycle were investigated. A total of 27 otherwise healthy patie nts previously scheduled for surgery were recruited after informed consent. An LH rise was detected, and CL were grouped according to age (Days 2-5 po st-LH-rise, early LP; Days 6-10, mid LP; Days 11-14, late LP). Using a semi quantitative reverse transcription-polymerase chain reaction assay, the PR- B mRNA levels, which were 100- to 1000-fold lower than PR-A/B mRNA, were 46 % lower (P < 0.05, n = 24) in mid LP, compared to early and late LP. CL tis sue levels of progesterone and PR-A/B protein levels were inversely correla ted to increasing CL age; i.e., significantly reduced levels were observed in the late LP (r(2) = 0.34, P < 0.01, n = 23). Expression of PR-A/B mRNA a s well as PR-A/B protein were detected by in situ hybridization and immunoh istochemistry, respectively. Both methods revealed a clear and distinct loc alization to cells in the steroidogenic layer of the CL. Freshly obtained m id-luteal CL cells were cultured in vitro, and media were analyzed for prog esterone concentrations after treatment by incremental doses of hCG and the stable PR antagonist mifepristone, alone or in combination. Mifepristone d id not per se alter progesterone synthesis, but when it was added in conjun ction with hCG, a dose-related inhibitory response was seen, with a maximal 47% reduction in progesterone output at a 10 mu M addition (P < 0.05, n = 3). Collectively, these data implicate a stimulatory role of progesterone r eceptor-mediated action in the steroidogenic cells of the human CL, which m ay serve as an important pathway for maintaining functional homeostasis dur ing early pregnancy.