Comparison of the Anti-LH/FSH-RH and Anti-Ovulatory Activities of [p-Phe², D-Leu⁶]-LH-RH and [O-Phe², D-Ala⁶]-LH-RH

Abstract

The anti-LH/FSH-RH and antiovulatory activities of [D-Phe², D-Leu⁶]-LH-RH and [D-Phe², D-Ala⁶]-LH-RH were compared in rats. Both peptides inhibited the LH and FSH release induced by LH-RH in immature male rats, but, 4 hr after the injection, [D-Phe², D-Leu⁶]-LH-RH still suppressed the LH and FSH release whereas the [D-Phe², D-Ala⁶]-LH-RH did not. When the peptides were administered in equal doses on the afternoon of the day of proestrus in 4-day cycling rats, [D-Phe², D-Leu⁶]-LH-RH more completely inhibited the ovulation occurring on the following morning than [D-Phe², D-Ala⁶]-LH-RH. Thus, the incorporation of D-Leucine into position six of the decapeptide chain gives a more potent inhibitor than that resulting from the insertion of D-Alanine.