DISSOCIATION OF RELAXIN AND PROGESTERONE SECRETION FROM THE PRIMATE CORPUS-LUTEUM BY ACUTE ADMINISTRATION OF A 3-BETA-HYDROXYSTEROID DEHYDROGENASE INHIBITOR DURING THE MENSTRUAL-CYCLE

The factors regulating relaxin production by the primate CL during spo ntaneous menstrual cycles and in early pregnancy are poorly understood , Since the CL produces steroids, notably progesterone, and expresses progesterone receptors, luteal progesterone may act locally to regulat e relaxin production, For the current study, either trilostane (600 mg daily)-a 3 beta-hydroxysteroid dehydrogenase inhibitor-or vehicle was administered to rhesus monkeys during the midluteal phase (Days 6 and 7) of spontaneous menstrual cycles to examine the effects of reduced luteal progesterone synthesis on relaxin secretion, Trilostane treatme nt reduced serum concentrations of progesterone within 3 h of initial administration and maintained low levels typical of the follicular pha se (< 1 ng/ml), causing premature menses without significant alteratio n in serum bioactive LH levels. Nevertheless, the patterns and levels of circulating relaxin, as measured by homologous macaque ELISA, were not different between trilostane- and vehicle-treated monkeys, with re laxin levels peaking in both groups by Day 13 of the luteal phase, To determine if chorionic gonadotropin (CG) injections simulating early p regnancy could stimulate relaxin production in a progesterone-depleted environment, trilostane or vehicle was administered as described abov e, followed by injections in increasing dosages of human (h) CG beginn ing 3 days after initial trilostane administration. Serum progesterone levels in trilostane-treated animals were significantly reduced prior to and during hCG treatment when compared with vehicle-treated animal s. However, serum relaxin levels were comparable between these groups; relaxin levels peaked approximately 10-fold above pre-hCG levels in b oth trilostane- and vehicle-treated animals, These data indicate that serum relaxin levels similar to those observed in control monkeys can be maintained during a period of very low progesterone concentrations during the spontaneous menstrual cycle and that even in a progesterone -depleted environment, CG remains an effective stimulator of relaxin p roduction. Therefore, it is unlikely that progesterone acts locally to promote the production and release of relaxin from the primate CL dur ing the menstrual cycle or early pregnancy.