Veldhuis J D, Iranmanesh A, Evans W S, Lizarralde G, Thorner M O, Vance M L
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
J Clin Endocrinol Metab. 1993 Mar;76(3):587-93. doi: 10.1210/jcem.76.3.8445014.
In the male rodent and primate, fasting or severe caloric restriction significantly decreases serum testosterone concentrations, putatively via inducing secondary hypogonadotrophism. To clarify this presumptive pathophysiology, we have used: 1) a high sensitivity immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay of LH; 2) blood sampling every 5 min for 24 h basally and every 10 min for 3 h after GnRH injection before and after a 5-day (water only) fast in eight healthy young men; and 3) deconvolution analysis to evaluate in vivo LH secretory burst frequency, amplitude, duration, and mass, and LH half-life simultaneously. We documented a 50% fall in serum total and free testosterone concentrations, and a 30% decrease in 24-h mean serum LH concentrations (viz., fed 3.0 +/- 0.47 vs. fasted 2.1 +/- 0.39 U/L, P = 0.043). Deconvolution analysis revealed preservation of LH secretory pulse frequency (fed 12.9 +/- 0.48 vs. fasted 12.6 +/- 0.78 secretory bursts/day, P = NS) during fasting-induced hypogonadotropism. The duration of computer-resolved LH secretory bursts, the interburst interval, and the calculated endogenous half-life of LH also did not change, whereas LH secretory burst mass declined significantly; viz. from 28 +/- 5 in the fed to 14 +/- 3.2 U/L of distribution volume/day in the fasted state (P = 0.034). In contrast, LH release after a 10 micrograms pulse of GnRH iv was enhanced during fasting in seven of the eight men. Fasting also decreased mean (24 h) serum TSH and PRL, increased cortisol, dehydroepiandrosterone sulfate and GH, and did not affect FSH concentrations or the radioiodinated albumen distribution space. In summary, in young men 5 days of nutrient deprivation selectively attenuates the mass of LH secreted per burst without altering LH secretory event frequency or LH half-life. We infer that decreased LH release per burst is due to decreased hypothalamic GnRH impulse strength, since LH release induced by a submaximally effective pulse of exogenous GnRH is amplified rather than attenuated.
在雄性啮齿动物和灵长类动物中，禁食或严格的热量限制会显著降低血清睾酮浓度，推测是通过诱导继发性性腺功能减退实现的。为了阐明这种假定的病理生理学机制，我们采用了以下方法：1）一种高灵敏度免疫放射分析方法，该方法与促黄体生成素（LH）的体外睾丸间质细胞生物测定法相关性良好；2）对8名健康年轻男性在5天（仅饮水）禁食前后，基础状态下每5分钟采血一次，共24小时，GnRH注射后每10分钟采血一次，共3小时；3）进行反卷积分析，以同时评估体内LH分泌脉冲频率、幅度、持续时间、总量以及LH半衰期。我们记录到血清总睾酮和游离睾酮浓度下降了50%，24小时平均血清LH浓度下降了30%（即，进食时为3.0±0.47 vs. 禁食时为2.1±0.39 U/L，P = 0.043）。反卷积分析显示，在禁食诱导的性腺功能减退期间，LH分泌脉冲频率保持不变（进食时为12.9±0.48 vs. 禁食时为12.6±0.78次分泌脉冲/天，P = 无显著差异）。计算机解析的LH分泌脉冲持续时间、脉冲间期以及计算得出的LH内源性半衰期也没有变化，而LH分泌脉冲总量显著下降；即从进食时的28±5降至禁食状态下的14±3.2 U/L分布容积/天（P = 0.034）。相反，8名男性中有7名在禁食期间静脉注射10微克GnRH脉冲后的LH释放增强。禁食还降低了平均（24小时）血清促甲状腺激素（TSH）和催乳素（PRL）水平，增加了皮质醇、硫酸脱氢表雄酮和生长激素（GH）水平，并且不影响促卵泡生成素（FSH）浓度或放射性碘化白蛋白分布容积。总之，在年轻男性中，5天的营养剥夺选择性地减弱了每次脉冲分泌的LH总量，而不改变LH分泌事件频率或LH半衰期。我们推断每次脉冲LH释放减少是由于下丘脑GnRH脉冲强度降低所致，因为外源性GnRH次最大有效脉冲诱导的LH释放是增强而非减弱的。
