人子宫内膜中 FSH 和 LH/hCG 受体的表达和功能的证据。
Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium.
机构信息
Mother-Infant Department, Institute of Obstetrics and Gynecology, University of Modena and Reggio Emilia and Clinica Eugin Modena, 41123, Modena, Italy.
Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Via G. Campi 287, 41125, Modena, Italy.
出版信息
J Assist Reprod Genet. 2018 Sep;35(9):1703-1712. doi: 10.1007/s10815-018-1248-8. Epub 2018 Jul 4.
PURPOSE
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) mediate intracellular functions by binding their specific protein G-coupled gonadotrophin receptor, respectively FSH receptor (FSHR) and LH/choriogonadotrophin receptor (LHCGR). Whereas the expression of FSHR and LHCGR in mammals was considered gonad-specific and cell-specific, studies identified gonadotrophin receptors in human female extragonadal reproductive tissues. This study aims to demonstrate that gonadotrophin receptors are expressed in endometrium and mediates intracellular functions.
METHODS
Collected endometria (n = 12) from healthy patients (mean age of 36 ± 6) were primary cultured for 24 h. The presence of gonadotrophin receptors was evaluated by RT-PCR followed by the sequencing of the resulted amplicons and by immunohistochemistry in original samples. Endometrial primary cultures were treated with increasing concentration (range 0-100 ng/ml) of either recombinant human LH (rhLH) or recombinant human FSH (rhFSH). Endometria controls had gonadotrophin replaced by the same volume of the culture medium. In gonadotrophin-treated samples, it was evaluated the intracellular cyclic adenosine monophosphate (cAMP) content by enzymatic immunoassay and the expression of steroidogenic genes by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).
RESULTS
The sequencing of the RT-PCR amplicons confirmed the presence of both gonadotrophin receptors and immunohistochemistry localized them on the membrane of endometrial glands cells throughout the glandular epithelium. The gonadotrophin-receptor complex was able to increase the intracellular cAMP in a dose-response and time-course manner and to induce steroidogenic genes expression.
CONCLUSION
This study demonstrates that both gonadotrophin receptors are expressed along the glandular epithelium of endometria and they mediate the effects of gonadotrophins on intracellular functions.
目的
卵泡刺激素（FSH）和黄体生成素（LH）通过分别结合其特异性蛋白 G 偶联促性腺激素受体 FSH 受体（FSHR）和 LH/绒毛膜促性腺激素受体（LHCGR）来介导细胞内功能。虽然 FSHR 和 LHCGR 在哺乳动物中的表达被认为是性腺特异性和细胞特异性的，但研究已经在人类女性生殖系统外的组织中鉴定出了促性腺激素受体。本研究旨在证明促性腺激素受体在子宫内膜中表达，并介导细胞内功能。
方法
收集来自健康患者（平均年龄 36±6 岁）的子宫内膜（n=12），并进行 24 小时的原代培养。通过 RT-PCR 检测促性腺激素受体的存在，随后对扩增子进行测序，并通过原始样本的免疫组织化学进行检测。用不同浓度（0-100ng/ml）的重组人 LH（rhLH）或重组人 FSH（rhFSH）处理子宫内膜原代培养物。在 rhLH 和 rhFSH 处理的样本中，通过酶免疫测定法评估细胞内环磷酸腺苷（cAMP）含量，并通过逆转录定量聚合酶链反应（RT-qPCR）评估类固醇生成基因的表达。
结果
RT-PCR 扩增子的测序证实了两种促性腺激素受体的存在，免疫组织化学定位它们在整个腺上皮的子宫内膜腺细胞的膜上。促性腺激素受体复合物能够以剂量反应和时间进程的方式增加细胞内 cAMP，并诱导类固醇生成基因的表达。
结论
本研究表明，两种促性腺激素受体都沿子宫内膜的腺上皮表达，并介导促性腺激素对细胞内功能的作用。
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