ANTIDE (NAL-LYS GNRH ANTAGONIST) SUPPRESSION OF PITUITARY-TESTICULAR FUNCTION AND SEXUAL-BEHAVIOR IN GROUP-LIVING RHESUS-MONKEYS

The ability of a Nal-Lys gonadotropin releasing-hormone antagonist (Antide) to suppress pituitary-testicular function and male sexual behavior was studied in seven group-living adult male rhesus monkeys. Each male received a single 15 mg/kg b.wt. subcutaneous injection of Antide dissolved in equal volumes of propylene glycol and sterile water. Prior to Antide treatment, and at two, four, and eight weeks after Antide, males received an IV bolus of GnRH (50 ng/kg) to assess pituitary and testicular function. For four weeks before and eight weeks after Antide treatment, blood samples and behavioral observations were collected three times weekly in a 74-member heterosexual group. Antide levels increased to more than 150 ng/ml 24 h postinjection and remained above 15 ng/ml for 30 days postinjection. Circulating LH and T were significantly reduced within 24 h following Antide, and remained significantly lower than pretreatment levels in all males for 5 weeks after Antide. T levels rose above 1 ng/ml while Antide levels were still significantly elevated in four males. Both LH and T returned to pretreatment levels by seven weeks post-Antide and then showed a second significant decrease during the eighth study week. Pituitary responsiveness to exogenous GnRH was reduced by Antide and remained below pretreatment levels eight weeks after Antide treatment. Testosterone secretion in response to exogenous GnRH was significantly reduced at two and four weeks post-Antide, but was at pretreatment levels by eight weeks after Antide. Male sexual behavior declined significantly within one week after Antide treatment, almost ceased completely by four weeks after Antide, and returned to pretreatment levels by seven weeks post-Antide. These results demonstrate a sustained suppression of pituitary-testicular function and male sexual behavior from a single injection of a GnRH antagonist. Data from administration of exogenous GnRH suggests that pituitary responsiveness remains reduced for longer than is evident from serum LH and T levels. The extremely rapid decline in male sexual behavior observed following pituitary-testicular suppression demonstrates the critical role androgens play in regulating male sexual behavior in a complex social context.