BIOASSAY OF SERUM LUTEINIZING HORMONE (LH) AND CHORIONIC GONADOTROPIN

血清促黄体激素（LH）和绒毛膜促性腺激素的生物测定

• 批准号: 3919207
• 负责人: M L DUFAU
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3919207
• 关键词: bioassay; blood chemistry; chorionic gonadotropin; dosage; enzyme linked immunosorbent assay; estradiol; estrogen inhibitor; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; human tissue; hypogonadism; laboratory rat; luteinizing hormone; peptide hormone analog; radioimmunoassay; tamoxifen; testosterone

1) Previous studies in human and experimental animals have suggested that sex steroid hormones may modulate the pituitary secretion of biologically active gonadotropin. We examine the role of E2 in biologically active LH secretion, in men subjected to steady state E2 infusion and feedback actions of endogenous E2 on spontaneous and exogenous GnRH stimulated pulsatile bioactive LH release. E2 suppressed mean circulating bioactive LH concentrations, with a consequent significant decline in the plasma bio/immune LH ratio. Conversely, antiestrogen treatment enhanced spontaneous bioactive LH pulse frequency, pulse amplitude, and intrapulse and interpulse bio/immune LH ratios. Low-dose pulsed injections of exogenous GnRH also increased plasma bio/immune LH ratios. However, tamoxifen attenuated the ability of exogenous GnRH to further enhance the bio/immune LH ratio, which suggests that endogenous LH release was already maximally enriched in LH bioactivity during antiestrogen administration. The ability of E2 to modulate specific properties of the LH pulse signal as well as its frequency may have significant implications in relation to target tissue function, and also reflect direct actions of estradiol on gonadotrope function, through influence the cellular processing and/or one or more aspects of terminal glycosylation of LH molecules. 2) In our early studies using a single large bolus of GnRH and/or continuous GnRH infusions were not able to disclose a stimulatory effect of exogenous GnRH on the plasma bio/immune LH ratio. In contrast, a schedule of two consecutive submaximal pulses (10 micrograms one hour apart) of exogenous GnRH did result in an immediate and preferential release of bioactive LH with a consequent increase in the plasma bio/immuno LH ratio. These findings might be explained by functional compartmentalization of releasable LH pools. 3) The dynamics of bioactive LH release in healthy older men (ages 60-75) have revealed significant attenuation of the pituitary's capacity to release biologically active gonadotropic hormone. The diminution of bioactive LH release could be unmasked by low-dose (10 micrograms) exogenous GnRH, or by antiestrogen treatment. Young and older healthy men exhibit similar mean basal plasma bioactive LH concentrations and spontaneous LH pulse properties. However, pituitary bioactive LH reserve is markedly attenuated in older men challenged with either exogenous GnRH or antiestrogen, indicating that healthy aging men manifest an impaired secretory reserve for biologically active LH release.

1)先前在人类和实验动物中的研究 表明性类固醇激素可以调节脑垂体 分泌具有生物活性的促性腺激素。 我们研究了 E2在生物活性LH分泌中的作用， 稳态E2输注和内源性E2对 自发性和外源性GnRH刺激的脉动性LH release. E2抑制平均循环生物活性LH 浓度，随后血浆中的浓度显著下降 生物/免疫LH比值。 相反，抗雌激素治疗增强了 自发生物活性LH脉冲频率、脉冲幅度和 脉冲内和脉冲间生物/免疫LH比值。 低剂量脉冲 注射外源性GnRH也可增加血浆生物/免疫LH 比率。 然而，他莫昔芬减弱了外源性 GnRH进一步提高生物/免疫LH比率，这表明 内源性LH释放已经最大程度地富集在LH中， 抗雌激素给药期间的生物活性。 E2的能力 以调制LH脉冲信号的特定特性， 其频率可能对以下方面产生重大影响： 靶组织功能，也反映了 雌二醇对促性腺激素功能的影响，通过影响细胞 的末端糖基化的一个或多个方面 LH分子。 2)在我们早期的研究中， GnRH和/或持续GnRH输注不能揭示 外源性GnRH对血浆生物/免疫LH的刺激作用 比例 相比之下，两个连续次最大值的时间表 外源性GnRH脉冲（10微克，间隔1小时）确实导致 在立即和优先释放生物活性LH中， 血浆生物/免疫LH比值随之增加。 这些 研究结果可能被解释为功能区室化， 可释放LH池。 3)促黄体生成素释放的动态变化 健康的老年男性（60-75岁）已经显示出显著的 垂体释放生物活性物质的能力减弱 活性促性腺激素 生物活性LH减少 低剂量（10微克）外源性 GnRH或抗雌激素治疗。 年轻和老年健康男性 表现出相似的平均基础血浆生物活性LH浓度， 自发LH脉冲特性。 然而，垂体生物活性LH 在老年男性中， 外源性促性腺激素释放激素或抗雌激素，表明健康的老年男性 表现出生物活性LH的分泌储备受损 release.