Mode of suppression of pituitary and gonadal function after acute or prolonged administration of a luteinizing hormone-releasing hormone antagonist in normal men.

LHRH antagonists compete with endogenous LHRH for binding to receptors on pituitary gonadotrophs and thereby inhibit gonadotropin secretion and, consequently, gonadal function. We studied the pituitary and gonadal suppression following single doses and short term administration (1–3 weeks) of a recently developed LHRH antagonist in normal men. First, the antagonist Nal-Glu ([Ac-d2Nal1, d4ClPhe2,d3Pal3,Arg5,dGlu6(AA),dAla10]LHRH), was given as a single sc injection to five normal men at three dose levels of 1, 5, and 20 mg (study I). Serum FSH, immunoreactive LH (IRLH), bioactive LH (bio-LH), testosterone, and estradiol were measured before and at frequent intervals for 48 h after Nal-Glu administration. Mean serum FSH decreased (P < 0.001) by 28.9 ± 5.4/ (±se), 38.2 ± 7.9/, and 44.5 ± 3.6/ after the 1-, 5-, and 20-mg doses, respectively. Mean serum IR-LH decreased (P < 0.001) by 39.0 ± 13.8/, 53.2 ± 10.0/, and 53.1 ± 14.4/ after the three doses. Serum bio-LH levels and the ratio of bio-LH/IR-LH decreased ...