INHIBITORY EFFECT OF A HIGHLY POTENT ANTAGONIST OF LH RELEASING HORMONE (SB-75) ON THE PITUITARY-GONADAL AXIS IN THE INTACT AND CASTRATED RAT

The biological potency of the new, highly potent antagonist [AC-D-Nal (2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] LH-RH (SB-75) on the pi tuitary-gonadal system of female castrated and intact ovulating rats w as tested. Administration of a single dose (50-100 mug/kg BW) of the a ntagonist SB-75 inhibited effectively the elevated gonadotrophin level s for 48 h. Pituitary LH and FSH content was not affected by SB-75 tre atment. When administered in the early afternoon of the proestrus to i ntact cycling rats, SB-75 blocked the preovulatory LH surge as well as the primary and secondary FSH surges. However, the secondary FSH surg e was not affected by SB-75 treatment when administered on the evening of proestrus suggesting its independence from the LH-RH mechanism. A group of ovariectomized rats was chronically treated with D-Trp6-LH-RH after having been pretreated by administration of a single dose of th e antagonist. The initial stimulatory release of LH and FSH initiated by injection of the LH-RH agonist was significantly reduced by pretrea tment with the LH-RH antagonist. We conclude that the LH-RH antagonist SB-75 may be used effectively in the field of reproductive dysfunctio n and endocrinological oncology and may become an invaluable physiolog ical probe in studying the hormonal dynamics of the reproductive endoc rine axis.