Blockade of the Pre-ovulatory LH Surge in Hamsters by an Inhibitory Analog of LH-RH

Abstract

The search continues for inhibitory analogs of LH-RH which have a high affinity for pituitary receptors and better resistance to degradation by plasma and tissue peptidases. Des-His2-desGlyl0-LH-RH ethylamide was the first analog reported to be a potent inhibitor of LH release induced by LH-RH both in vivo with immature male rats (1) or ovariectomized steroid-blocked rats (2) and in vitro (3). Subsequently, other analogs of LH-RH having an enhanced ability to inhibit the LH and FSH released by LH-RH have been reported (4, 5). Recently, D-Phe2-D-Leu6-LH-RH was synthesized in our laboratories based on the inhibitory analog D-Phe2-LH-RH (6) and the powerful gonadotropin-releasing analog D-Leu6-LH-RH (7). It showed a greatly prolonged suppression of LH release in response to LH-RH in immature male rats (8). The surge of circulating LH on the afternoon of proestrus or of midcycle has been associated with an increase in pituitary sensitivity to LH-RH (9-1 1) and also with an increase of LH-RH activity as determined by bioassay (12) or radioimmunoassay in plasma (1 3). Since the administration of an antiserum to synthetic LH-RH suppressed the cyclic surge of LH and FSH in proestrous rats and prevented ovulation (14), we studied the ability of D-Phe2-D-Leu6-LH-RH to suppress the cyclic surge of peripheral LH on the day of proestrus and observed its effects on ovulation in cycling hamsters.