Comparison of the anti-LH/FSH-RH and anti-ovulatory activities of (D-Phe2, D-Leu6)-LH-RH and (D-Phe2, D-Ala6)-LH-RH

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.