Prevention of gonadotropin-releasing hormone antagonist induced luteal regression by concurrent exogenous pulsatile gonadotropin administration in monkeys.

We studied the effects of a gonadotropin-releasing hormone (GnRH) antagonist given in midluteal phase. Monkeys received the antagonist (n = 6), [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-GnRH: hydrochloride or vehicle (n = 5). Absent luteinizing hormone (LH) pulsatility, diminished progesterone (P) secretion (P less than 0.01), luteal phase truncation and premature menstruation were observed in all receiving the antagonist. To investigate the site of action, four females received pulsatile exogenous human menopausal gonadotropins (hMG) concurrently, whereby P secretion was sustained and premature menstruation was averted. Equivalent treatment using "pure" FSH, failed to sustain P levels and timely menstruation occurred, confirming the continuing dependence of the corpus luteum on LH. The antagonist acts by central suppression and in turn, diminishes P biosynthesis. LH is luteotropic, since pulsatile LH (hMG), not "pure" FSH, prevented luteolysis.