Titrating luteinizing hormone replacement to sustain the structure and function of the corpus luteum after gonadotropin-releasing hormone antagonist treatment in rhesus monkeys

These studies were designed to identify 1) a regimen of a third generation GnRH antagonist that abolishes primate luteal function, and 2) the amount o f LK replacement required to maintain the structure and functional life spa n of the corpus luteum of the menstrual cycle after GnRH antagonist treatme nt. A single injection of antide at 3 or 5 mg/kg BW on day 6 of the luteal phase suppressed serum progesterone levels within 1 day of treatment, but l evels recovered within 4 days. Administration of antide (3 mg/kg) for 3 day s (luteal days 6-8) reduced (P < 0.05) serum progesterone below 1 ng/mL and maintained these low levels far the entire sampling period; in subsequent experiments, all monkeys received this antide regimen. Fixed doses (5, 10, or 20 IU) of recombinant human LH administered at 8-h intervals during and after antide treatment stimulated progesterone production in a dose-depende nt manner; these monkeys menstruated earlier than controls regardless of tr eatment group. Replacement with an escalating dose regimen (5-20 IU) of LH resulted in typical serum progesterone and relaxin levels throughout a lute al phase of normal length. Corpora lutea removed on day 10 from monkeys tre ated with antide alone had decreased wet weight (P < 0.05) and few large lu teal cells; coadministration of the escalating dose regimen of LH maintaine d luteal structure similar to that seen in time-matched controls. Antide-on ly treatment increased progesterone receptor (PR) messenger ribonucleic aci d, but decreased PR immunostaining in luteal tissue; the escalating dose re gimen of LH maintained PR messenger ribonucleic acid and immunostaining sim ilar to those in controls. This study indicates that during GnRH antagonist administration, an escalating dose regimen of LH replacement is optimal fo r maintenance of the structure and functional life span of the primate corp us luteum.