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.
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