Veldhuis J D, Iranmanesh A, Demers L M, Mulligan T
Department of Internal Medicine, National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
J Clin Endocrinol Metab. 1999 Oct;84(10):3506-14. doi: 10.1210/jcem.84.10.6076.
To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21-34) and 8 older men (ages 62-72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution analysis, and the orderliness of the FSH release process via quantitated the approximate entropy statistic. Statistical analysis revealed that healthy older men manifest dual neuroendocrine hypersecretory mechanisims; specifically, a 2-fold increase in the basal (nonpulsatile) FSH secretion rate, and a concurrent 50% amplification of FSH secretory burst mass (and amplitude). The regularity or orderliness of ad seriatim FSH release is preserved in older individuals. We postulate that higher basal FSH secretion in older men is a consequence of reduced testosterone negative feedback, whereas amplified FSH secretory burst mass reflects net enhanced stimulation of gonadotrope cells by endogenous FSH secretagogues (e.g. GnRH and/or activin). The foregoing specific mechanisms driving heightened FSH secretion in older men contrast with the lower-amplitude pulsatility and more disorderly patterns of LH release in the same individuals. Thus, the present data illuminate an age-dependent disparity in the disruption of FSH neuroregulation in the aging male.
为了评估健康老年男性血清促卵泡生成素(FSH)浓度选择性(单向性)升高背后的神经内分泌机制,我们在11名年轻男性(21 - 34岁)和8名老年男性(62 - 72岁)夜间每隔2.5分钟采集一次血液样本。采用基于化学发光的自动化高灵敏度检测法对血清FSH浓度进行定量分析。通过去卷积分析估计基础和脉冲式FSH分泌率,并通过定量近似熵统计量来评估FSH释放过程的有序性。统计分析表明,健康老年男性表现出双重神经内分泌分泌亢进机制;具体而言,基础(非脉冲式)FSH分泌率增加了2倍,同时FSH分泌脉冲量(及幅度)同步放大了50%。老年个体中FSH依次释放的规律性或有序性得以保留。我们推测,老年男性基础FSH分泌增加是睾酮负反馈减弱的结果,而FSH分泌脉冲量放大反映了内源性FSH促分泌素(如促性腺激素释放激素和/或激活素)对促性腺激素细胞的净刺激增强。上述驱动老年男性FSH分泌增加的具体机制与同一人群中促黄体生成素(LH)释放幅度较低且模式更紊乱形成对比。因此,目前的数据揭示了衰老男性中FSH神经调节破坏存在年龄依赖性差异。