Ihibition of the pre-ovulatory proestrous gonadotropin surge, ovulation and pregnancy with a peptide analogue of luteinizing hormone releasing hormone

Abstract

D-[PHE]-2-D[ALA]-6-LRH (Wy-18,185), an analogue of synthetic hypothalamic LRH, was evaluated for its anti-fertility properties. The compound dampens the preovulatory proestrous surge of serum LH and FSH in rats, is an active anti-ovulatory agent in both rats and rabbits and prevents pregnancy when administered pre-coitally to rats. Additionally, the compound suppresses the ovulatory event in rats only during the cycle in which it is acutely administered, does not interfere with the rat vaginal cycle and is devoid of any effects on body, ovarian and uterine weights when given acutely. The compound is a moderate LRH agonist in rats but does not induce ovulation in rats or rabbits.

PIP: The antifertility properties of D-(PHE)2-D-(ALA) 6-LRH (Wy-18, 185), a peptide analogue of synthetic hypothalamic luteinizing hormone-releasing hormone (LH-RH), were evaluated in the rat and rabbit. The compound was found to diminish the preovulatory surge of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rats, inhibited ovulation in rats and rabbits, and had a contraceptive effect in rats when administered prior to mating. The anti-ovulatory effect in rats was observed only in cycles in which the drug was acutely administered. Wy-18, 185 does not interrupt the vaginal cycle in the rat, and has no effect in acute doses on body, ovarian, and uterine weights. In rats, Wy-18, 815 is a moderate LH-RH agonist, but does not induce ovulation in either species. The results demonstrate that a LH-RH antagonist can significantly depress the pre-ovulatory, proestrus hypophysical LH and FSH surge, inhibit ovulation, and prevent pregnancy in rats.