REDUCED-SIZE ANTAGONISTS OF LUTEINIZING-HORMONE-RELEASING HORMONE ACTIVE IN-VITRO

A series of reduced-size analogs of LHRH was designed with the length varying from nine to two amino acids. These compounds were tested in v itro for the LH suppression in cultured rat pituitary cells treated wi th 1 ng of LHRH. The best analogs were also tested in vivo for their a ntiovulatory activity in rats. It appeared that terminal amino acids a s well as the presence of Arg or ILys in the sequence are both crucial for the antagonism. The most potent antagonist in this series was a h eptapeptide, AcDNal-Ser-Tyr-DNal-Leu-Arg-ProNHEt, which completely inh ibited LH release at the dose 0.1 mu g and inhibited ovulation at 1000 mu g/rat. For fragments shorter than heptapeptide the inhibition of L H release was observed at the dose 100 mu g of the analog.