Direct effect of the luteinizing hormone releasing hormone analog D-Trp⁶-Pro⁹-Net-LHRH on rat ovarian steroidogenesis

The luteinizing hormone releasing hormone analog D-Trp⁶-Pro⁹-Net-LHRH (LHRH(a)) inhibits rat ovarian estradiol secretion. To determine whether LHRH(a) decreases serum estradiol concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly ovarian estradiol biosynthesis, we examined the effects of LHRH(a) on the activities of 5 key ovarian steroidogenic enzymes. Fifty hypophysectomized, gonadotropin-treated rats were given either LHRH(a) (1 μg/day) or saline sc during 7 days. The LHRH(a) treated animals exhibited a significant decrease in serum estradiol when compared with the control group (461 ± 30 vs 31 ± 5 pg/ml, mean ± SE, P<0.001). The changes in estradiol concentration were associated with decreases in ovarian weight (372 ± 19 vs 185 ± 11 mg, P<0.001) and in the microsomal enzyme activities of 3β-hydroxysteroid dehydrogenase (156 ± 5 vs 53 ± 4 nmol/mg prot/min, P<0.001), 17 hydroxylase (4.7 ± 0.8 vs 3.7 ± 0.7 nmol/mg prot/min, P<0.002), 17,20 desmolase (279 ± 14 vs 50 ± 7 pmol/mg prot/min, P<0.001), 17 ketosteroid reductase (132 ± 11 vs 6 ± 1 nmol/mg prot/min, P<0.001), and aromatase (19 ± 1.5 vs 0.9 ± 0.1 nmol/mg prot/min, P<0.001) in LHRH(a) treated animals. These findings indicate that LHRH(a) can inhibit directly rat ovarian estradiol biosynthesis.