Evans R M, Doelle G C, Alexander A N, Uderman H D, Rabin D
J Clin Endocrinol Metab. 1984 May;58(5):862-7. doi: 10.1210/jcem-58-5-862.
LHRH agonist analogs induce hypogonadism in man but the mechanism is uncertain. To evaluate this, we treated 13 normal men with 50 micrograms/day D-Trp6,Pro9-NEt LHRH (LHRHA) for periods up to 8 weeks and measured (1) patterns of endogenous gonadotropin and testosterone secretion, (2) gonadal response to exogenous human LH infusions, and (3) gonadotropin and testosterone responses to hourly bolus doses of LHRH. Seven men were evaluated with frequent sampling for 12-h periods every 4 week during treatment with LHRHA. Before treatment, all had three to four spikes of LH in 12 h. On the first day of treatment, the response to LHRHA was tested in four of the men, and there were significant increases in LH, FSH, and testosterone. After 4 weeks, all men had dramatic decreases in mean testosterone levels and blunted or absent gonadotropin responses to acute injection of LHRHA. Mean gonadotropin levels at 4 and 8 weeks were variable; values lower than pretreatment basal levels were found in three men, while unchanged or higher values were found in the remaining four. The pulsatile pattern of LH secretion, characteristic among these men before treatment, was lost during LHRHA therapy. Forty-eight-hour constant infusion of human LH in four other analog-treated men resulted in increases in serum testosterone comparable to those in untreated men. Pulsatile administration of native sequence LHRH to two other men during chronic treatment with LHRHA failed to elicit demonstrable responses in serum gonadotropin or testosterone levels. LHRHA produced a qualitative change in the pattern of LH release from the pituitary. Mean basal LH levels varied during treatment, but the normal pulsatile pattern was diminished. The gonadotropin response to pulsatile administration of LHRH was lost during chronic treatment with LHRHA, but the Leydig cell remained responsive to exogenous human LH. Thus, the locus of action of the analog appears to be at the level of the pituitary in man.
促性腺激素释放激素（LHRH）激动剂类似物可导致男性性腺功能减退，但其机制尚不清楚。为评估此机制，我们对13名正常男性给予每日50微克的D-色氨酸6、脯氨酸9-乙基-LHRH（LHRHA）治疗，疗程长达8周，并测定了：（1）内源性促性腺激素和睾酮的分泌模式；（2）性腺对外源性人促黄体生成素（LH）输注的反应；（3）促性腺激素和睾酮对每小时推注剂量LHRH的反应。7名男性在LHRHA治疗期间，每4周进行一次为期12小时的频繁采样评估。治疗前，所有人在12小时内有3至4次LH峰值。治疗第一天，对其中4名男性测试了对LHRHA的反应，LH、促卵泡生成素（FSH）和睾酮均显著升高。4周后，所有男性的平均睾酮水平显著下降，对急性注射LHRHA的促性腺激素反应减弱或消失。4周和8周时的平均促性腺激素水平各不相同；3名男性的值低于治疗前基础水平，而其余4名男性的值未改变或更高。这些男性治疗前特有的LH分泌脉冲模式在LHRHA治疗期间消失。另外4名接受类似物治疗的男性进行48小时人LH持续输注后，血清睾酮升高幅度与未治疗男性相当。在LHRHA慢性治疗期间，对另外两名男性进行天然序列LHRH的脉冲给药，未能引起血清促性腺激素或睾酮水平的明显反应。LHRHA使垂体LH释放模式发生了质的变化。治疗期间平均基础LH水平有所不同，但正常的脉冲模式减弱。在LHRHA慢性治疗期间，对脉冲式给予LHRH的促性腺激素反应消失，但睾丸间质细胞对外源性人LH仍有反应。因此，该类似物的作用位点似乎在男性的垂体水平。
