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促性腺激素释放激素(GnRH)的药效学。II. GnRH给药方式改变女性垂体促黄体生成素的分泌

Pharmacodynamics of gonadotropin-releasing hormone (GnRH). II. Pattern of GnRH delivery alters pituitary luteinizing hormone secretion in women.

作者信息

Handelsman D J, Boylan L M

机构信息

Department of Medicine, University of Sydney, Australia.

出版信息

J Clin Endocrinol Metab. 1988 Jul;67(1):175-9. doi: 10.1210/jcem-67-1-175.

DOI:10.1210/jcem-67-1-175
PMID:3132482
Abstract

The pulse frequency, amplitude, and mode of administration of GnRH all influence gonadotropin secretion and, ultimately, pituitary-gonadal function. We studied plasma LH responses to repetitive iv administration of GnRH given hourly for 5 h as a 2-microgram rapid (less than 15 s) bolus dose or a 2-microgram dose infused for 15 min of each hour in seven women deficient in endogenous GnRH and sex steroids. Plasma LH levels, measured at 10-min intervals throughout the 5-h period, rose more briskly (pattern X time course interactions: F = 3.33; P less than 0.0001) to higher levels overall (F = 11.7; P = 0.014) after rapid bolus GnRH administration than after GnRH infusion. Plasma FSH levels increased during both modes of delivery, with higher responses to rapid bolus GnRH administration (P = 0.005). Plasma estradiol levels did not change during either 5-h study. We conclude that the pattern of delivery of GnRH is a determinant of pituitary LH and FSH secretion in untreated hypogonadotropic women, and therefore, that alterations in the GnRH wave form and/or peak plasma GnRH concentrations consequent upon different rates of GnRH entry into the blood-stream may explain the different responses that occur when GnRH is given by different routes.

摘要

促性腺激素释放激素(GnRH)的脉冲频率、幅度及给药方式均会影响促性腺激素的分泌,最终影响垂体-性腺功能。我们研究了7名内源性GnRH和性类固醇缺乏的女性,她们每小时静脉注射GnRH共5小时,每次注射2微克,分别采用快速(小于15秒)推注剂量或每小时输注15分钟的2微克剂量,观察血浆促黄体生成素(LH)的反应。在整个5小时期间,每隔10分钟测量一次血浆LH水平,快速推注GnRH后,LH水平总体上升更快(模式X时间过程交互作用:F = 3.33;P < 0.0001),且升至更高水平(F = 11.7;P = 0.014),而GnRH输注后则不然。两种给药方式下血浆促卵泡生成素(FSH)水平均升高,快速推注GnRH给药后的反应更高(P = 0.005)。在5小时的研究期间,血浆雌二醇水平均未发生变化。我们得出结论,GnRH的给药方式是未治疗的低促性腺激素性女性垂体LH和FSH分泌的决定因素,因此,不同速率的GnRH进入血流后,GnRH波形和/或血浆GnRH峰值浓度的改变可能解释了不同给药途径给予GnRH时出现的不同反应。

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引用本文的文献

1
Update on pulsatile luteinizing hormone-releasing hormone therapy in males with idiopathic hypogonadotropic hypogonadism and delayed puberty.特发性低促性腺激素性性腺功能减退和青春期延迟男性的脉冲式促黄体生成素释放激素治疗进展
J Endocrinol Invest. 1991 May;14(5):419-29. doi: 10.1007/BF03349093.