Pavlou S N, Interlandi J W, Wakefield G, Island D P, Rivier J, Vale W, Kovacs W J
J Clin Endocrinol Metab. 1987 May;64(5):1070-4. doi: 10.1210/jcem-64-5-1070.
The ability of prolonged administration of a LHRH antagonist, [Ac-delta 3Pro1,4F-D-Phe2,D-Trp3,6]LHRH (4F-antagonist), to suppress serum gonadotropin and testosterone levels was studied in normal men. The 4F-antagonist was given either as a continuous 13.3 micrograms/kg X h sc infusion for 72 h or as intermittent sc injections of 100 micrograms/kg every 6 h for 7 days. Serum FSH, LH, and testosterone levels decreased in the period immediately following initiation of 4F-antagonist administration. However, an escape toward baseline levels for each of these hormones occurred during prolonged antagonist administration. When men receiving the continuous infusion were challenged with iv bolus doses of 50 micrograms LHRH, the response of LH after the first 12 h of 4F-antagonist administration was similar to that before its administration. This gonadotropin and testosterone escape suggests that, at the doses used, the inhibitory action of the antagonist on gonadotropin secretion is progressively lost. The initial decrease in androgen levels could serve to augment endogenous LHRH release, which, in turn, overcomes the pituitary effects of the antagonist, or to augment endogenous LH secretion directly. These results demonstrate that the pituitary can escape from the suppressive effects of prolonged LHRH antagonist administration and partially restore serum gonadotropin and testosterone levels to normal in man.
在正常男性中研究了长效施用促性腺激素释放激素（LHRH）拮抗剂[Ac-δ3Pro1,4F-D-Phe2,D-Trp3,6]LHRH（4F-拮抗剂）抑制血清促性腺激素和睾酮水平的能力。4F-拮抗剂以13.3微克/千克×小时的剂量连续皮下输注72小时，或每6小时皮下注射100微克/千克，共7天。在开始施用4F-拮抗剂后的即刻，血清促卵泡激素（FSH）、促黄体生成素（LH）和睾酮水平下降。然而，在长期施用拮抗剂期间，这些激素中的每一种都出现了向基线水平的回升。当接受连续输注的男性静脉注射50微克LHRH大剂量冲击时，在施用4F-拮抗剂的前12小时后LH的反应与其施用前相似。这种促性腺激素和睾酮的回升表明，在所使用的剂量下，拮抗剂对促性腺激素分泌的抑制作用逐渐丧失。雄激素水平的最初下降可能会增强内源性LHRH的释放，进而克服拮抗剂对垂体的作用，或者直接增强内源性LH的分泌。这些结果表明，垂体能够摆脱长期施用LHRH拮抗剂的抑制作用，并使男性血清促性腺激素和睾酮水平部分恢复正常。
