Absence of gonadotropin-releasing hormone receptors in human gonadal tissue
Absence of gonadotropin-releasing hormone receptors in human gonadal tissue
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人类性腺组织中缺乏促性腺激素释放激素受体
作者：
R. Clayton;I. Huhtaniemi
下丘脑肽促性腺激素释放激素 (GnRH) 及其合成激动剂类似物 (GnRH-A) 的抗生育特性已在啮齿类动物、猴子和人类身上得到反复证明（参见参考文献 1 的综述）。在所有研究的物种中，GnRH 的这种作用最初归因于性腺类固醇生成的“脱敏”，这是由于重复施用 GnRH 或 GnRH-A2-5 后内源性促性腺激素的高循环水平引起的睾丸和卵巢中促性腺激素受体的丧失所致。最近，这些肽对卵巢颗粒 6,7 和黄体 8-10 以及睾丸 Leydig11-13 细胞的额外直接抑制作用已被确定。这种对性腺类固醇生成的直接抑制是通过各自靶组织中特定的高亲和力 GnRH 受体介导的8,9,12,14。这些受体表现出与啮齿动物垂体前叶组织中的 GnRH 受体 (GnRH-R) 相同的特征 9,12,14,15。在寻找性腺 GnRH-R 天然配体的过程中，从大鼠卵巢 16 和睾丸 17,18 以及猴睾丸间质液 18 中分离出了一种具有生物活性的“GnRH 样”肽。这些发现表明，啮齿类动物性腺中会产生一种 GnRH 样肽，该肽与性腺 GnRH-R 相互作用后，可作为类固醇生成的局部调节剂，从而调节生殖能力。如果人类存在类似情况，则在人类睾丸和卵巢中也应该可以检测到 GnRH-R。我们在此报告，我们无法检测到放射性标记的 GnRH-A 与人黄体或睾丸或猴睾丸的任何结合。相比之下，在成人和胎儿的垂体前叶组织中检测到 GnRH-R。因此，我们认为 GnRH 对灵长类动物生殖功能的直接抑制作用不太可能。此外，这种重要的物种差异凸显了重新评估某些啮齿动物模型的必要性，这些模型旨在研究灵长类动物，特别是人类的生殖生理学。
The antifertility nature of the hypothalamic peptide gonadotropin releasing hormone (GnRH) and its synthetic agonist analogue (GnRH-A) has been repeatedly demonstrated in rodents, monkeys and humans (see ref. 1 for review). In all species studied, this action of GnRH was initially attributed to ‘desensitization’ of gonadal steroidogenesis due to loss of gonadotropin receptors in the testis and ovary, induced by high circulating levels of endogenous gonadotropins achieved following repeated administration of GnRH or GnRH-A2–5. Recently, an additional, direct inhibitory action of these peptides on ovarian granulosa6,7 and luteal8–10 and testicular Leydig11–13 cells has been defined. This direct inhibition of gonadal steroidogenesis is mediated through specific high-affinity GnRH receptors in the respective target tissues8,9,12,14. These receptors exhibit identical characteristics to GnRH receptors (GnRH-R) in rodent anterior pituitary tissue9,12,14,15. In the search for a naturally occurring ligand for gonadal GnRH-R, a biologically active ‘GnRH-like’ peptide has been isolated from rat ovary16 and testis17,18, and from monkey testis interstitial fluid18. These findings suggest the production in rodent gonads of a GnRH-like peptide which, following interaction with gonadal GnRH-R, serves as a local modulator of steroidogenesis, and hence of reproductive capacity. If a similar situation exists in humans, GnRH-R should be detectable also in the human testis and ovary. We report here that we have been unable to detect any binding of radiolabelled GnRH-A to human corpus luteum or testis, or to the monkey testis. In contrast, GnRH-R were detected in adult and fetal human anterior pituitary tissue. Thus, we suggest that a direct inhibitory action of GnRH on primate reproductive function is unlikely. Furthermore, this important species difference highlights the need for a re-evaluation of certain rodent models designed to investigate primate, and especially human, reproductive physiology.
黄体生成素释放因子及其激动剂对培养的人颗粒细胞的影响。
影响因子：
6.7
作者：
Casper,RF;Erickson,GF;Rebar,RW;Yen,SS
通讯作者：
Yen,SS
恒河猴 (Macacca mulatta) 黄体中缺乏 LH-RH 结合位点。
DOI：
10.1210/jcem-53-1-214
发表时间：
1981
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Asch,RH;VanSickle,M;Rettori,V;Balmaceda,JP;Eddy,CA;Coy,DH;Schally,AV
通讯作者：
Schally,AV