Direct Effect of the Luteinizing Hormone Releasing Hormone Analog D-Trp⁶-Pro⁹-Net-LHRH on Rat Ovarian Steroidogenesis

Summary

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 ug/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.

Key-Words:

Ovaries - Luteinizing Hormone Releasing Hormone - Steroidogenesis - Enzyme Activity - Estradiol