GnRH agonists and antagonists stimulate recovery of fertility in irradiated LBNF1 rats

The goal of this study was to determine whether both gonadotropin-releasing hormone (GnRH) agonists and antagonists could enhance fertility in rats gi ven sterilizing doses of irradiation, to quantify the levels of fertility, and to measure their relative effectiveness in stimulating recovery of sper matogenesis. Irradiated rats were treated with either the GnRH agonist Lupr on or the GnRH antagonist Cetrorelix, which have different mechanisms of ac tion. The antagonist suppressed luteinizing hormone (LH), reducing intrates ticular testosterone from 75 ng/g-testis to about 5 ng/g-testis, whereas th e agonist reduced intratesticular testosterone only moderately to about 20 ng/g-testis, presumably by direct action on the Leydig cell since LH was el evated. These differences were reflected in Leydig cell morphology. When ho rmone treatment was started immediately after 3.7-Gy irradiation, fertility was normal at week 20 in the agonist-treated rats and was near normal in a ntagonist-treated rats, whereas irradiated-only rats were sterile. At week 22 in the GnRH antagonist-treated rats, testicular weights and sperm counts were maintained at greater than 80% of control values; in GnRH agonist-tre ated rats, they were slightly but significantly lower than in GnRH antagoni st-treated rats, and in irradiated-only rats, they were very low. When the treatment was initiated 10 weeks after 5-Gy irradiation, after spermatogene sis had ceased, fertility was restored at week 30 to subnormal levels in 83 % of GnRH agonist- and 50% of GnRH antagonist-treated rats. Testis weights and sperm counts were restored to about 50% and 20% of control levels, resp ectively. The percentages of tubules with differentiated germ cells were hi gher in all groups of antagonist-treated rats than in those of agonist-trea ted rats. Thus, both GnRH agonists and antagonists produced dramatic recove ry of spermatogenesis and fertility in irradiated rats, although there were differences in mechanism and perhaps also in effectiveness.