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[睾丸对人绒毛膜促性腺激素(hCG)刺激的类固醇生成反应动力学。V. hCG诱导的17-20裂解酶阻断是一种年龄依赖性现象,可通过hCG预处理诱导]

[Kinetics of the steroidogenic response of the testis to stimulation by hCG. V. Blockade of 17-20 lyase induced by hCG is an age-dependent phenomenon inducible by pre-treatment with hCG].

作者信息

Forest M G, Roulier R

出版信息

Ann Endocrinol (Paris). 1984;45(4-5):281-90.

PMID:6535446
Abstract

The series of events, evidenced in animals after a single injection of human chorionic gonadotrophin (hCG): down-regulation of LH/hCG membrane receptors, uncoupling between receptors and the adenylate cyclase, also includes a blockade of testicular steroidogenesis beyond cyclic-AMP formation, including an inhibition of the 17 alpha-hydroxylase-17, 20-desmolase enzymatic complex. This complex phenomenon, named hCG-induced testicular desensitization also occurs in adult men. Since it is not known if and when these effects are initiated during sexual maturation, we have investigated the kinetics of responses of plasma testosterone (T), its two immediate precursors, delta 4-androstenedione (delta 4) and 17 alpha-hydroxprogesterone (OHP), and 17 beta-estradiol (E2) for a week after a single injection of hCG given at the same dosage (100 IU/kg body weight) in subjects not yet exposed to adult levels of endogenous LH, ie prepubertal boys and untreated hypogonadotrophic hypogonadic (HH) adult men. The HH subjects have been restudied after 3 months of a weekly injection of the hCG at the same dosage. In immature individuals, the effect of hCG on testicular steroidogenisis was strikingly different from that observed previously in adults: in the former, whether prepubertal boys or untreated HH adults, a single hCG injection induced a progressive and substantial rise in plasma T, maximal at 96-120 h, a modest and late rise in E2, but no significant change in delta 4 or OHP. In contrast, in adult men there is a dissociation between the responses of plasma T and delta 4 (maximal at about 72 h) to hCG and those of OHP and E2 which peak at about 24 h. After 3 months of hCG-treatment the adult pattern was induced in HH patients: early and significant rise in OHP and E2. This suggests that a pre-exposure to LH/hCG is necessary for hCG-induced testicular desensitization, at least for its enzymatic expression. A stimulatory effect of hCG on a testicular aromatase and an inhibitory effect on the 17, 20-desmolase are observed concomitantly in relation to age or to previous gonadotropin environment. It still remains uncertain to conclude that the former effect is directly responsible for the latter.

摘要

单次注射人绒毛膜促性腺激素(hCG)后在动物身上出现的一系列事件包括:促黄体生成素/人绒毛膜促性腺激素(LH/hCG)膜受体下调、受体与腺苷酸环化酶解偶联,还包括在环磷酸腺苷(cAMP)形成之外对睾丸类固醇生成的阻断,其中包括对17α-羟化酶-17,20-裂解酶酶复合物的抑制。这种复杂现象,即hCG诱导的睾丸脱敏,在成年男性中也会发生。由于尚不清楚这些效应在性成熟过程中是否以及何时开始,我们研究了在未接触成年水平内源性LH的受试者(即青春期前男孩和未经治疗的低促性腺激素性性腺功能减退(HH)成年男性)中,单次注射相同剂量(100 IU/kg体重)hCG后一周内血浆睾酮(T)、其两个直接前体Δ4-雄烯二酮(Δ4)和17α-羟孕酮(OHP)以及17β-雌二醇(E2)的反应动力学。对HH受试者在每周注射相同剂量hCG 3个月后进行了再次研究。在未成熟个体中,hCG对睾丸类固醇生成的影响与之前在成年人中观察到的显著不同:在前者中,无论是青春期前男孩还是未经治疗的HH成年男性,单次注射hCG都会导致血浆T逐渐大幅升高,在96 - 120小时达到最大值,E2有适度且延迟的升高,但Δ4或OHP无显著变化。相比之下,在成年男性中,血浆T和Δ4(约72小时达到最大值)对hCG的反应与OHP和E2的反应不同,后者在约24小时达到峰值。在HH患者中进行3个月的hCG治疗后,诱导出了成年模式:OHP和E2早期且显著升高。这表明至少对于其酶表达而言,预先接触LH/hCG是hCG诱导睾丸脱敏所必需的。关于年龄或先前促性腺激素环境,同时观察到hCG对睾丸芳香化酶有刺激作用,对17,20-裂解酶有抑制作用。目前仍不确定前者的作用是否直接导致了后者的结果。

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