Effects of Gonadotropin-Releasing Hormone Treatment on Ovarian Steroid Production during Midpregnancy 1 2

Abstract

Abstract

During the second half of pregnancy, ovarian testosterone (T) through its conversion to estradiol (E) promotes progesterone (P) synthesis by the ovary which maintains the pregnancy. To determine if the administration of gonadotropin-releasing hormone (GnRH) disrupts pregnancy by suppressing ovarian production of T or its conversion to E, rats were treated from Day 11 through Day 18 of pregnancy with 50 or 100 μg/day of GnRH or 1, 5, or 10 μg/day of a GnRH agonist (GnRH-Ag; WY-40972) using an osmotic minipump. Rats were bled daily from the jugular vein under light ether anesthesia and on Days 14 or 18 of pregnancy both jugular and ovarian blood samples were obtained. While the GnRH-Ag treatment at the dose of 5 or 10 μg/day terminated pregnancy within 48 hr as indicated by vaginal bleeding, 1 μg/day terminated pregnancy more slowly. Neither dose of GnRH was effective in terminating pregnancy through Day 18. By Day 14, peripheral levels of plasma P in rats treated with 0, 1, 5, or 10 μg of GnRH-Ag were 97 ± 9, 24 ± 1, 13 ± 3, and 8 ± 1, respectively. In the same groups, levels in the ovarian vein were 3205 ± 633, 1317 ± 273, 360 ± 113, and 228 ± 73 ng/ml. By Day 18, serum P levels in the peripheral circulation and in the ovarian vein were declining even more dramatically. Daily administration of P (4 mg) and E (0.5 μg) simultaneously with GnRH-Ag at the dose of 5 μg/day from Days 11 through 14 reversed the abortifacient effect of GnRH-Ag and maintained pregnancy indicating that the GnRH-Ag effect is not directly on the uterus. Ovarian vein levels of T on Days 14 or 18 of pregnancy were either not different from controls at 1407 ± 163 or 1476 ± 122 pg/ ml, respectively, or increased dramatically in certain groups. Ovarian vein levels of E were either not different from controls at 292 ± 13 pg/ml on Day 14 or increased significantly in rats treated at the dose of 1 μg/day of GnRH-Ag. However by Day 18, treatment with GnRH-Ag at all doses suppressed ovarian secretion of E. These results suggest that while the GnRH-Ag induces abortion in rats by suppressing ovarian production of P, this abortifacient effect is not due to a fall in ovarian T levels nor to its aromatization to E in the ovary.