In vivo inhibition of LH release by a synthetic antagonist of lh-releasing hormone (LH-RH)

The anti LH releasing hormone (LH RH) activity of des His² desGly¹⁰ LH RH ethylamide (antagonist I), an analogue of LH RH, was studied in several animal systems. An i.v. infusion of antagonist I for 2 hr significantly inhibited LH release in response to the administration of LH RH in ovariectomized, estrogen and progesterone treated (OEP) rats and intact adult male rats. In OEP rats, a good dose response inhibition curve was found. Similarly, a quick injection of antagonist I was able to inhibit partially the LH release induced by LH RH in OEP rats. In addition, the high levels of serum LH in rats ovariectomized for 2 mth were lowered by the infusion of antagonist I. In cycling female rats, 2 injections of antagonist I blocked ovulation induced by exogenous LH RH in the second day of diestrous and chronic administration of antagonist I delayed spontaneous ovulation for at least 48 hr. The synthesis of this antagonist of LH RH capable of partially blocking LH release may be a first step toward the development of birth control methods based on synthetic peptides.