Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary
Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary
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DOI：
10.1210/jc.82.8.2720
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发表时间：
1997-08-01
影响因子：
5.8
通讯作者：
Yen, SSC
中科院分区：
文献类型：
--
作者：
Asakura, H;Zwain, IH;Yen, SSC
最近，免疫反应性促肾上腺皮质激素释放因子（IrCRF）的存在下，在人卵巢的卵泡膜基质细胞和CRF的能力，抑制雌激素的产生，人颗粒细胞在体外已被报道。为了了解卵巢CRF的功能作用，需要对人类卵巢CRF系统进行表征，该系统包括CRF、1型CRF受体（CRF-R1）和高亲和力CRF结合蛋白（CRF-BP）。因此，我们已经研究了卵巢CRF系统和细胞分布的这些蛋白质及其信使核糖核酸（mRNA），分别使用免疫组织化学和原位杂交。10例绝经前妇女行子宫切除联合卵巢切除术后的正常卵巢组织中，IrCRF及其mRNA定位于小窦卵泡和成熟卵泡的卵泡膜细胞中。在两个阶段的卵泡基质细胞中也检测到低丰度的IrCRF和mRNA。编码CRF的基因在成熟卵泡中的表达比在小的有腔卵泡中更显著。CRF-R1 mRNA仅在成熟卵泡的卵泡膜细胞中表达，在小窦卵泡中表达量适中，颗粒细胞中不表达CRF和CRF-R1 mRNA及蛋白。IrCRF-BP，而不是它的转录，检测到在卵泡膜细胞和管腔的毛细血管的卵泡膜/基质室成熟卵泡。用逆转录-PCR证实了人卵泡中不存在CRF-BP基因转录本，表明所检测到的IrCRF-BP不是来自卵巢转录本，并提示IrCRF-BP和卵泡膜区毛细血管管腔的存在来源于外周循环。成熟卵泡的卵泡膜细胞，相对于小窦卵泡，表现出强烈的免疫染色和17 α-羟化酶（P450 c17）的mRNA信号，表明雄激素的生物合成。我们的结论是，人卵巢的卵泡膜室包含一个CRE系统赋予CRF和CRF-R1和血液来源的CRF-BP。颗粒细胞缺乏CRF系统。CRF、CRF-R1和17 α-羟化酶蛋白和基因表达强度随卵泡成熟而平行增加，表明卵巢内CRF系统可能在雄激素生物合成中起自分泌作用，并对颗粒细胞的雌激素产生产生下游效应。卵巢CRF系统的功能性可能取决于循环中CRF-BP的相对存在，这是由于其与CRF竞争CRF受体的能力。
Recently, the presence of immunoreactive corticotropin-releasing factor (IrCRF) in the thecal-stromal cells of the human ovary and the ability of CRF to suppress estrogen production by human granulosa cells in vitro have been reported. To understand the functional role of ovarian CRF requires characterization of the human ovarian CRF system, which includes CRF, type 1 CRF receptor (CRF-R1), and the high affinity CRF-binding protein (CRF-BP). Accordingly, we have examined the ovarian CRF system and the cellular distribution of these proteins and their messenger ribonucleic acids (mRNAs) using immunohistochemistry and in situ hybridization, respectively. Normal ovaries from 10 premenopausal women undergoing hysterectomy with ovariectomy were used in the analyses.IrCRF and its mRNA were localized in thecal cells of small antral and mature follicles. A low abundance of IrCRF and mRNA was also detected in stromal cells of both stages of follicles. Expression of the gene encoding CRF was more prominent in mature follicles than in small antral follicles. CRF-R1 mRNA signal was found exclusively in thecal cells of mature follicles and moderately in small antral follicles, Granulosa cells were devoid of CRF and CRF-R1 mRNAs and proteins. The IrCRF-BP, but not its transcript, was detected in thecal cells and lumen of capillary vessels of the thecal/stromal compartment of mature follicles. The absence of CRF-BP gene transcript in human ovarian follicles was confirmed by reverse transcription-PCR, indicating that the IrCRF-BP detected is not derived from the ovarian transcript and suggesting that the presence of IrCRF-BP and luman of capillary vessels in the thecal compartment originates From the peripheral circulation. Thecal cells of mature follicles, relative to those of small antral follicles, exhibited an intensive immunostaining and mRNA signal for 17 alpha-hydroxylase (P450c17) indicative of androgen biosynthesis. We conclude that the thecal compartment of the human ovary contains a CRE system endowed with CRF and CRF-R1 and the blood-derived CRF-BP. Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17 alpha-hydroxylase proteins and gene expression with follicular maturation suggest that the intraovarian CRF system may play an autocrine role in androgen biosynthesis with a downstream effect on estrogen production by the granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of circulating CRF-BP by virtue of its ability to compete with CRF for the CRF receptor.