Veldhuis J D, Johnson M L, Dufau M L
J Clin Endocrinol Metab. 1987 Jun;64(6):1275-82. doi: 10.1210/jcem-64-6-1275.
We used the rat interstitial cell testosterone (RICT) bioassay to assess biological LH activity secreted in response to endogenous and low dose exogenous GnRH pulses in normal men. The absence of nonspecific plasma effects in the LH bioassay was demonstrated by the finding of undetectable levels of LH bioactivity despite low but measurable immunoactivity in 10 hypogonadotropic men. Moreover, bolus injections of human LH in 6 hypogonadotropic men defined a curvilinear relationship between plasma bioactive and immunoactive LH concentrations, in which the extrapolated concentration of plasma bioactive LH at a zero dose of immunoactive LH was indistinguishable from zero. Zero bioactive LH intercepts were also found when physiological bio- and immunoactive LH concentrations derived from 7 intensively sampled normal men were subjected to linear regression using 2-dimensional error fitting. In these men, exogenous low dose (10 micrograms) iv GnRH administration resulted in preferential release of bioactive LH, with a consequent significant increase in the median plasma bio- to immunoactive (bioimmuno) LH ratio. This pattern mimicked that of endogenous LH pulsatility, in which median intrapulse bio:immuno LH ratios were significantly higher than median interpulse ratios in the same individuals (P = 0.006). Increases in spontaneous plasma bio:immuno LH ratios were not attributable to spurious rises in bioactive LH concentrations associated with decreases in serum immunoactive LH levels. Rather, sample cross-correlation analyses demonstrated positive correlations between bio- and immunoactive LH at lags of 0-40 min, indicating that both hormones increased or decreased concomitantly. These results demonstrate that LH is secreted physiologically in pulses of increased biological activity, presumably reflecting the release of a functionally compartmentalized LH pool relatively enriched in biologically active hormone. Accordingly, evaluation of the plasma bio:immuno LH ratio can provide a useful and sensitive index of qualitative changes in the LH molecule in response to endogenous (spontaneous) and exogenous GnRH stimulation.
我们采用大鼠间质细胞睾酮（RICT）生物测定法，评估正常男性体内响应内源性和低剂量外源性促性腺激素释放激素（GnRH）脉冲分泌的生物促黄体生成素（LH）活性。在10名低促性腺激素性男性中，尽管免疫活性较低但可测量，却未检测到LH生物活性水平，这证明了LH生物测定中不存在非特异性血浆效应。此外，对6名低促性腺激素性男性进行人LH推注，确定了血浆生物活性LH浓度与免疫活性LH浓度之间的曲线关系，其中免疫活性LH零剂量时血浆生物活性LH的外推浓度与零无差异。当对7名密集采样的正常男性的生理生物活性和免疫活性LH浓度进行二维误差拟合线性回归时，也发现了生物活性LH截距为零。在这些男性中，静脉注射低剂量（10微克）外源性GnRH导致生物活性LH优先释放，从而使血浆生物活性与免疫活性（生物免疫）LH比值中位数显著增加。这种模式与内源性LH脉冲性相似，即同一受试者脉冲内生物：免疫LH比值中位数显著高于脉冲间期比值（P = 0.006）。血浆生物：免疫LH比值的自发升高并非归因于与血清免疫活性LH水平降低相关的生物活性LH浓度的假性升高。相反，样本互相关分析表明，生物活性LH与免疫活性LH在0 - 40分钟滞后时呈正相关，表明两种激素同时升高或降低。这些结果表明，LH以生物活性增加的脉冲形式生理性分泌，推测这反映了功能上分隔的LH池的释放，该池相对富含生物活性激素。因此，评估血浆生物：免疫LH比值可提供一个有用且敏感的指标，用于反映LH分子响应内源性（自发）和外源性GnRH刺激的定性变化。
