Functional evidence for divergent receptor activation mechanisms of luteotrophic and luteolytic events in the human corpus luteum

Using a dispersed human luteal cell culture model, progesterone synthesis f ollowing treatment by incremental doses of human chorionic gonadotrophin (H CG) and the stable prostaglandin F-2 alpha (PGF(2 alpha)) analogue cloprost enol, alone or in combination, was related to corpora lutea (CL) mRNA trans cript abundance coding for the luteinizing hormone (LH)/HCG receptor (LH-R) and PGF(2 alpha)-receptor (FP) by semi-quantitative reverse transcription- polymerase chain reaction (RT-PCR) in 33 otherwise healthy women, scheduled for surgery due to benign conditions. CL were grouped according to age, ba sed on the occurrence of a preovulatory LH surge where post-LH days 2-5 wer e designated as early luteal phase; days 6-10 as mid-luteal phase and days 11-14 as late luteal phase. When exposed to HCG, maximal progesterone outpu t was raised 2.2-fold (P = 0.08, n = 5) compared with untreated controls in the early CL, while it increased 5.7- and 4.6-fold in the mid- and late gr oups respectively (P < 0.05, n = 4 mid-luteal phase, n = 3 late luteal phas e). This stimulation pattern was found to be concordant with the value of m RNA coding for LH-R in all groups (n = 6 early luteal phase, n = 5 mid-lute al phase, n = 6 late luteal phase). The integrated response to HCG and clop rostenol showed a dose-dependent 60% inhibition of progesterone production, but only in late luteal phase luteal cells (P < 0.01, n = 3). FP mRNA valu es were lowest in early luteal phase, and increased with the age of the CL. Interestingly, lowest CL tissue concentrations of the natural FP agonist P GF(2 alpha), were found during mid-luteal phase while it increased again 1. 6-fold during late luteal phase (P < 0.05, n = 8 versus mid-luteal phase, n = 6). Collectively, these data demonstrate that (i) the extrinsic function al control (or rescue of CL in the event of pregnancy) occurs when the sens itivity towards LH/HCG is maximal; and (ii) the demise of CL function is me diated via an acquisition of sensitivity towards the intrinsic luteolytic s ignal, PGF(2 alpha), in the ageing CL.