Santen R J, Bardin C W
J Clin Invest. 1973 Oct;52(10):2617-28. doi: 10.1172/JCI107454.
The demonstration that luteinizing hormone (LH) release from the pituitary is episodic rather than constant raises fundamental questions regarding the physiologic control of pulsatile LH secretion and its possible alteration in patients with gonadal disorders. To evaluate this mode of LH secretion, quantitative means of analyzing LH pulse amplitude, frequency, shape, and area were established and utilized to study normal subjects and patients with disorders of gonadotropin secretion. Similar patterns of LH secretion were observed in normal men, in women during the follicular phase of the menstrual cycle, and in patients with hyper- and hypogonadotropism, hirsuitism, and amenorrhea (mean pulse amplitude 39-179% from nadir to peak, frequency 2.7-3.9 secretory spikes/6 h). These observations suggested that the pattern of LH secretion is similar in both normal individuals and in those with a variety of pathologic conditions. By contrast, the pattern of pulsatile secretion appeared to differ in the following conditions. LH pulses of higher amplitude (333+/-170%) and lower frequency (1.6+/-0.24 SEM/6 h) characterized the secretory patterns of women during the luteal phase of the menstrual cycle, suggesting that gonadal steroids may modulate LH pulses. LH pulses of low amplitude (26+/-2.1%) and frequency (1.3+/-0.36/6 h) were observed in women with anorexia nervosa. Either integrated LH levels or a mean LH level determined from multiple samples provided a more accurate reflection of gonadotropin secretion than the use of single LH measurements. With multiple sampling over 6 h, it was possible to reduce the 95% confidence limit of LH estimates from +/-50-90 to +/-12%. This allowed normal subjects to be distinguished from patients with low or moderately elevated LH levels in whom gonadotropin levels in single samples were often in the "normal range."Several aspects of the physiologic control of pulsatile LH secretion were studied. The concordance of follicle-stimulating hormone (FSH) with LH pulses progressively increased as LH pulse height increased (P < 0.01) suggesting possible hypothalamic mediation of gonadotropin pulses. Measurement of the "apparent half-life" of LH after secretory spikes revealed half times of 34-233 min. It is likely that this variability was attributable to at least two phenomena: (a) constant low level LH secretion that continued after certain secretory episodes but not others; (b) variable mixing of newly secreted LH into at least two pools. The alpha adrenergic-blocking agents, chlorpromazine and phentolamine, failed to block LH secretory spikes at doses sufficient to result in a 30 mm drop in systolic blood pressure in normal men.
促黄体生成素（LH）从垂体的释放是间歇性而非持续恒定的，这一现象引发了关于LH脉冲式分泌的生理控制及其在性腺疾病患者中可能发生改变的基本问题。为评估LH的这种分泌模式，已建立并采用了定量分析LH脉冲幅度、频率、形状和面积的方法，用于研究正常受试者以及促性腺激素分泌紊乱的患者。在正常男性、月经周期卵泡期的女性以及促性腺激素水平过高或过低、多毛症和闭经患者中观察到了相似的LH分泌模式（平均脉冲幅度从最低点到峰值为39 - 179%，频率为2.7 - 3.9次分泌峰/6小时）。这些观察结果表明，正常个体和患有各种病理状况的个体的LH分泌模式相似。相比之下，在以下情况下，脉冲式分泌模式似乎有所不同。月经周期黄体期女性的分泌模式以较高幅度（333±170%）和较低频率（1.6±0.24 SEM/6小时）的LH脉冲为特征，这表明性腺类固醇可能调节LH脉冲。神经性厌食症女性观察到低幅度（26±2.1%）和低频率（1.3±0.36/6小时）的LH脉冲。与单次测量LH相比，整合LH水平或从多个样本确定的平均LH水平能更准确地反映促性腺激素的分泌情况。通过在6小时内进行多次采样，有可能将LH估计值的95%置信区间从±50 - 90降至±12%。这使得能够区分正常受试者与LH水平低或中度升高的患者，在这些患者中，单次样本中的促性腺激素水平通常处于“正常范围”。对LH脉冲式分泌的生理控制的几个方面进行了研究。随着LH脉冲高度增加，促卵泡激素（FSH）与LH脉冲的一致性逐渐增加（P < 0.01），这表明促性腺激素脉冲可能由下丘脑介导。测量分泌峰后LH的“表观半衰期”，发现半衰期为34 - 233分钟。这种变异性可能至少归因于两种现象：（a）某些分泌事件后持续存在但其他事件后不存在的持续低水平LH分泌；（b）新分泌的LH在至少两个池中的可变混合。α肾上腺素能阻滞剂氯丙嗪和酚妥拉明，在足以使正常男性收缩压下降30 mmHg的剂量下，未能阻断LH分泌峰。
