Evidence that gonadotropin-releasing hormone II is not a physiological regulator of gonadotropin secretion in mammals
Evidence that gonadotropin-releasing hormone II is not a physiological regulator of gonadotropin secretion in mammals
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DOI：
10.1046/j.1365-2826.2003.01065.x
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发表时间：
2003-09-01
影响因子：
3.2
通讯作者：
Lincoln, GA
中科院分区：
文献类型：
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作者：
Gault, PM;Maudsley, S;Lincoln, GA
当给哺乳动物高剂量时，促性腺激素释放激素 (GnRH)-II 会刺激黄体生成素 (LH) 和卵泡刺激素 (FSH) 的分泌，并且这种作用被认为是通过促性腺激素上表达的 GnRH-II 受体介导的。本研究使用两种选择性 GnRH-I 受体拮抗剂来检验另一种假设，即 GnRH-II 通过 GnRH-I 受体发挥作用，引起促性腺激素分泌。拮抗剂抗肽用于表征受体中继，因为它是一种纯体外拮抗剂，基于转染哺乳动物 GnRH-I 和 GnRH-II 受体的 COS-7 细胞中的磷酸肌醇反应，并且在体内，在我们的性不活跃绵羊模型中，有效拮抗单次注射 250 ng GnRH-I 的促性腺激素释放作用。在一系列绵羊研究中，抗肽 (i) 阻断单次注射 GnRH-II 后的急性 LH 反应（20 杯抗肽：10 杯 GnRH-II）； (ii) 阻断在 36 小时内每 2 小时注射 GnRH-II 的急性、脉动 LH 反应和 FSH 启动反应（100 杯抗肽/8 小时：4 杯 GnRH-II/2 小时）； (iii) 在 10 天内，每 4 小时注射一次 GnRH-II，长期阻断脉动 LH 反应和显着的 FSH 启动反应（75 杯抗肽/8 小时：4 杯 GnRH-II/4 小时）。在最后两个实验中，先前显示可激动哺乳动物 GnRH-II 受体的 GnRH-I 拮抗剂 135-18 阻断了 GnRH-I (250 ng) 的促性腺激素释放作用，但单独给予时未能引发 LH 反应，并且同时施用 GnRH-II (250 ng) 未能改变 GnRH-I (50-500 ng) 的 LH 释放作用。这些数据因此支持我们的假设。根据其他文献，GnRH-II 十肽不太可能是哺乳动物促性腺激素的天然调节剂。
Gonadotropin-releasing hormone (GnRH)-II stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH-II receptor expressed on gonadotropes. This study used two selective GnRH-I receptor antagonists to test the alternative hypothesis that GnRH-II acts through the GnRH-I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor-relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS-7 cells transfected with either mammalian GnRH-I and GnRH-II receptors and, in vivo , potently antagonized the gonadotropin-releasing effect of a single injection of 250 ng GnRH-I in our sexually inactive sheep model. In a series of studies in sheep, antide (i) blocked the acute LH response to a single injection of GnRH-II (20 mug antide: 10 mug GnRH-II); (ii) blocked both the acute, pulsatile LH response and the FSH priming response to 2-hourly injections of GnRH-II over 36 h (100 mug antide/8 h: 4 mug GnRH-II/2 h); and (iii) chronically blocked both the pulsatile LH response and the marked FSH priming response to 4-hourly injections of GnRH-II over 10 days (75 mug antide/8 h: 4 mug GnRH-II/4 h). In two final experiments, the GnRH-I antagonist 135-18, shown previously to agonize the mammalian GnRH-II receptor, blocked the gonadotropin-releasing effects of GnRH-I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH-II (250 ng) failed to alter the LH-releasing effect of GnRH-I (50-500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH-II decapeptide is a native regulator of the gonadotrope in mammals.