Suppression of testicular activity by a GnRH agonist in hypophysectomized, gonadotropin-treated mice

Although it is believed that the suppressive effect of GnRH agonist on the testes in mediated, at least in part, through its direct action on the testes in rats, such direct action was considered to appear in rats alone and in no other species, including mice, primates and humans. To reexamine such species' specific direct action of GnRH agonists, the effect of a potent GnRH agonist, D-Leu6-GnRH (GnRH-A), on testicular activity was investigated in hypophysectomized, gonadotropin-treated mice. Thirteen days after hypophysectomy the testicular weight had decreased to 20% of that of intact mice. Daily injection of 1 IU of HCG and 0.1 microgram of HMG for 10 days restored the testicular weight to 50% of that of the control animals. Daily sc injections of 1, 0.1 or 0.01 micrograms of GnRH-A (in addition to HCG and HMG) slightly but significantly prevented restoration of testicular weight by exogenous gonadotropins in hypophysectomized mice. A more dramatic effect of GnRH-A was observed in serum testosterone levels. Hypophysectomy resulted in a nearly 96% reduction in serum testosterone level. Treatments with HCG and HMG raised the levels to those found in intact mice. Daily injections of GnRH-A resulted in a marked reduction of testosterone levels at all doses of GnRH-A tested to those corresponding to hypophysectomized, vehicle-treated animals. Daily injection of 1 microgram of GnRH-A also reduced both testicular weight and testosterone levels, but the magnitudes of these reductions were smaller than those observed in hypophysectomized, gonadotropin-treated mice. The results clearly indicated that chronic treatment with GnRH-A reduces testicular function through direct action in mice under the experimental conditions employed.