Oestrogen induces rhythmic expression of the Kisspeptin-1 receptor GPR54 in hypothalamic gonadotrophin-releasing hormone-secreting GT1-7 cells.
Oestrogen induces rhythmic expression of the Kisspeptin-1 receptor GPR54 in hypothalamic gonadotrophin-releasing hormone-secreting GT1-7 cells.
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雌激素在下丘脑性促性腺营养蛋白释放激素分泌GT1-7细胞中诱导Kisspeptin-1受体GPR54的节奏表达。
DOI：
10.1111/j.1365-2826.2011.02188.x
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发表时间：
2011-09
影响因子：
3.2
通讯作者：
Chappell PE
中科院分区：
文献类型：
--
作者：
Tonsfeldt KJ;Goodall CP;Latham KL;Chappell PE
雌激素刺激的排卵前促性腺激素激增的时间调节方式尚未完全了解。哺乳动物排卵需要大量的促性腺激素释放激素（GnRH），它是由下丘脑中的专门神经元释放的。浪涌调节是由卵巢雌激素（E2）反馈介导的-作为一个负信号，直到下午早些时候的发情前期，在这一点上，它刺激强劲的GnRH释放增加。多线的证据表明，在浪涌产生的昼夜节律钟的作用，但在整个下丘脑中基底的几个神经元群体的内源性振荡器的存在下复杂的阐明昼夜节律调节的潜在机制。在这项研究中，我们提出，内源性振荡器内的GnRH神经元的雌激素调制，引起GnRH浪涌分泌。这可能发生的一种机制是通过已知的GnRH刺激物的受体的上调，例如kisspeptin的同源受体GPR 54。通过对mRNA和蛋白丰度模式的分析，我们发现高水平的E2在体外引起GPR 54的昼夜节律表达谱，并且时钟的内源性GnRH振荡器的破坏抑制了这种作用。此外，虽然Kisspeptin给药GT 1 -7细胞不会导致激增水平的分泌，但我们观察到用正反馈水平的E2处理的GT 1 -7细胞的GnRH分泌增加。在体外神经元模型系统中的这些结果表明了一种可能的机制，即受体表达水平，从而GnRH对kisspeptin的敏感性，可能会在发情前期发生显着变化。通过这种方式，卵巢E2升高可能增加接吻肽能紧张，同时增加GnRH神经元对这种神经肽的敏感性，以实现最大峰释放。
Oestrogen-stimulated preovulatory gonadotrophin surges are temporally regulated in a way which remains not fully understood. Mammalian ovulation requires surges of gonadotrophin-releasing hormone (GnRH), released from specialized neurones in the hypothalamus. Surge regulation is mediated by ovarian oestrogen (E2) feedback- acting as a negative signal until the early afternoon of the pro-oestrus phase, at which point it stimulates robust increases in GnRH release. Multiple lines of evidence suggest a role for the circadian clock in surge generation, but the presence of endogenous oscillators in several neuronal populations throughout the mediobasal hypothalamus complicates elucidating the underlying mechanisms of circadian regulation. In this study, we propose that endogenous oscillators within GnRH neurones are modulated by oestrogen to elicit GnRH surge secretion. One mechanism by which this may occur is through the upregulation of receptors of known stimulators of GnRH, such as kisspeptin’s cognate receptor, GPR54. Through analysis of mRNA and protein abundance patterns, we found that high levels of E2 elicit circadian expression profiles of GPR54 in vitro, and that disruption of endogenous GnRH oscillators of the clock dampens this effect. Additionally, while kisspeptin administration to GT1-7 cells does not result in surge-level secretion, we observed increased GnRH secretion from GT1-7 cells treated with positive feedback levels of E2. These results in this in vitro neuronal model system suggest a possible mechanism whereby receptor expression levels, and thus GnRH sensitivity to kisspeptin, may change dramatically over the pro-oestrus day. In this way, elevated ovarian E2 may increase kisspeptidergic tone while simultaneously increasing GnRH neuronal sensitivity to this neuropeptide for maximal surge release.
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DOI：
10.4161/cc.9.6.11046
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gery S;Koeffler HP
通讯作者：
Koeffler HP
影响因子：
5.3
作者：
Christian, Catherine A.;Moenter, Suzanne M.
通讯作者：
Moenter, Suzanne M.
影响因子：
4.1
作者：
Castellano, J. M.;Navarro, V. M.;Tena-Sempere, M.
通讯作者：
Tena-Sempere, M.
影响因子：
29
作者：
Grimaldi B;Bellet MM;Katada S;Astarita G;Hirayama J;Amin RH;Granneman JG;Piomelli D;Leff T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
影响因子：
1.8
作者：
Adachi, Sachika;Yamada, Shunji;Maeda, Kei-Ichiro
通讯作者：
Maeda, Kei-Ichiro