Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats:: In vivo and in vitro studies
Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats:: In vivo and in vitro studies
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DOI：
10.1159/000092753
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发表时间：
2005-01-01
影响因子：
4.1
通讯作者：
Pinilla, Leonor
中科院分区：
文献类型：
--
作者：
Fernandez-Fernandez, Rafael;Tena-Sempere, Manuel;Pinilla, Leonor
生长激素释放肽是一种胃源性促食欲肽，参与能量稳态，最近被认为是一种生殖方面的激素释放肽，并且在大鼠模型中已经证明生长激素释放肽对促黄体生成激素（LH）分泌的主要抑制作用。然而，ghrelin对促性腺轴的调节作用仍然很少评价。我们在此报告了生长激素释放肽对雌性大鼠LH和促卵泡激素（FSH）分泌的影响的详细分析，使用体内和体外方法相结合。脑室内给药的生长激素释放肽（3 nmol/大鼠）引起了显着的抑制LH分泌的周期性雌性大鼠在整个发情周期（发情前期下午，发情期，动情后期），以及在卵巢切除的女性。在良好的协议，促性腺激素释放激素（GnRH）分泌的卵巢切除女性的下丘脑片段显着抑制生长激素释放肽。与此相反，生长激素释放肽剂量依赖性刺激基础LH和FSH分泌垂体组织在体外，一种现象，被证明依赖于发情周期的阶段，因为它既没有检测到在发情期，也没有观察到卵巢切除术后。相反，促性腺激素释放激素刺激的LH分泌在体外持续抑制生长素释放肽，无论阶段的周期，而刺激的FSH分泌仅抑制生长素释放肽在发情期。此外，在垂体中观察到生长激素促分泌素受体（GHS-R）1a（即功能性生长素释放肽受体）mRNA水平的周期性波动，在发情期和发情后期值较低。然而，GHS-R1 a mRNA水平在卵巢切除术后保持不变。总之，我们的数据说明了生长激素释放肽对促性腺激素轴的复杂作用模式，在中枢（下丘脑）水平和GnRH诱导的促性腺激素分泌上具有主要的抑制作用，但对基础LH和FSH分泌具有直接的刺激作用。总体而言，我们的研究结果进一步证明了生长激素释放肽的生殖作用，这可能与能量平衡和生殖的综合控制有关。版权所有（c）2005 S. Karger AG，巴塞尔。
A reproductive facet of ghrelin, a stomach-derived orexigenic peptide involved in energy homeostasis, has been recently suggested, and predominantly inhibitory effects of ghrelin upon luteinizing hormone (LH) secretion have been demonstrated in rat models. Yet, the modulatory actions of ghrelin on the gonadotropic axis remain scarcely evaluated. We report herein a detailed analysis of the effects of ghrelin upon LH and follicle-stimulating hormone (FSH) secretion in the female rat, using a combination of in vivo and in vitro approaches. Intracerebroventricular administration of ghrelin (3 nmol/rat) evoked a significant inhibition of LH secretion in cyclic female rats throughout the estrous cycle (proestrus afternoon, estrus, metestrus), as well as in ovariectomized females. In good agreement, gonadotropin-releasing hormone (GnRH) secretion by hypothalamic fragments from ovariectomized females was significantly inhibited by ghrelin. In contrast, ghrelin dose-dependently stimulated basal LH and FSH secretion by pituitary tissue in vitro; a phenomenon that was proven dependent on the phase of estrous cycle, as it was neither detected at estrus nor observed after ovariectomy. Conversely, GnRH-stimulated LH secretion in vitro was persistently inhibited by ghrelin regardless of the stage of the cycle, whereas stimulated FSH secretion was only inhibited by ghrelin at estrus. In addition, cyclic fluctuations in mRNA levels of growth hormone secretagogue receptor (GHS-R)1a, i.e. the functional ghrelin receptor, were observed in the pituitary, with low values at estrus and metestrus. GHS-R1a mRNA levels, however, remained unchanged after ovariectomy. In summary, our data illustrate a complex mode of action of ghrelin upon the gonadotropic axis, with predominant inhibitory effects at central (hypothalamic) levels and upon GnRH-induced gonadotropin secretion, but direct stimulatory actions on basal LH and FSH secretion. Overall, our results further document the reproductive role of ghrelin, which might be relevant for the integrated control of energy balance and reproduction. Copyright (c) 2005 S. Karger AG, Basel.