Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary
Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary
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DOI：
10.1210/jc.2002-021196
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发表时间：
2003-02-01
影响因子：
5.8
通讯作者：
Tena-Sempere, M
中科院分区：
文献类型：
--
作者：
Gaytan, F;Barreiro, ML;Tena-Sempere, M
Ghrelin是一种由28个氨基酸组成的多肽，是生长激素促分泌素受体（GHS-R）的内源性配体。除了其标志性的中枢神经内分泌作用的GH分泌和食物摄入的控制，最近出现了一个意想不到的生殖方面的生长激素释放肽，因为这种分子及其同源受体的表达已被证明在大鼠睾丸。然而，这种信号系统是否存在于人类性腺中仍有待评估。在这项研究中，我们已经评估了生长激素释放肽及其功能性受体，即la型GHS-R的存在和细胞位置，在周期的人卵巢通过免疫组织化学方法使用特定的多克隆抗体。在卵巢门间质细胞中表现出强烈的ghrelin免疫染色。与此相反;生长素释放肽信号在任何发育阶段的卵泡中均未检测到，也不存在于非常早期发育的新形成的黄体（CL）中。然而，明确观察到特定的生长激素释放肽免疫反应在年轻和成熟的CL，而表达的肽消失在退化的黄体组织。关于同源受体，卵巢表达的GHS-R1 a蛋白显示了更广泛的组织分布模式，在卵母细胞以及体细胞卵泡细胞中具有可检测的特异性信号;来自年轻、成熟、年老和退化CL的黄体细胞;和间质门细胞。特别值得注意的是，卵泡GHS-R1 a肽表达促进卵泡发育，在健康的有腔卵泡的颗粒层和卵泡膜层中具有更强的免疫染色。总之，我们的研究结果是第一次证明，生长激素释放肽及其功能性la型受体表达在周期性人类卵巢细胞位置的不同模式。人卵巢内生长激素释放肽信号系统的两种组分（配体和受体）的存在开辟了这种新分子在生理和病理生理条件下对卵巢功能的潜在调节作用的可能性。
Ghrelin is a novel 28-amino acid peptide identified as the endogenous ligand for the GH secretagogue receptor (GHS-R). Besides its hallmark central neuroendocrine effects in the control of GH secretion and food intake, an unexpected reproductive facet of ghrelin has recently emerged because expression of this molecule and its cognate receptor has been demonstrated in rat testis. However, whether this signaling system is present in human gonads remains to be evaluated. In this study, we have assessed the presence and cellular location of ghrelin and its functional receptor, namely the type la GHS-R, in the cyclic human ovary by means of immunohistochemistry using specific polyclonal antibodies. Strong ghrelin immunostaining was demonstrated in ovarian hilus interstitial cells. In contrast; ghrelin signal was not detected in ovarian follicles at any developmental stage, nor was it present in newly formed corpora lutea (CL) at very early development. However, specific ghrelin immunoreactivity was clearly observed in young and mature CL, whereas expression of the peptide disappeared in regressing luteal tissue. Concerning the cognate receptor, ovarian expression of GHS-R1 a protein showed a wider pattern of tissue distribution, with detectable specific signal in oocytes as well as somatic follicular cells; luteal cells from young, mature, old, and regressing CL; and interstitial hilus cells. Of particular note, follicular GHS-R1a peptide expression paralleled follicle development with stronger immunostaining in granulosa and theca layers of healthy antral follicles. In conclusion, our results are the first to demonstrate that ghrelin and its functional type la receptor are expressed in the cyclic human ovary with distinct patterns of cellular location. The presence of both components (ligand and receptor) of the ghrelin signaling system within the human ovary opens up the possibility of a potential regulatory role of this novel molecule in ovarian function under physiological and pathophysiological conditions.