Lack of evidence for functional luteinising hormone chorionic gonadotropin receptors in non-pregnant human endometrial stromal cells

Lack of evidence for functional luteinising hormone chorionic gonadotropin receptors in non-pregnant human endometrial stromal cells
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缺乏关于非妊娠人子宫内膜基质细胞中功能性黄体生成激素绒毛膜促性腺激素受体的证据

DOI:
10.1101/2022.01.05.474837
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Mann O
Mann O
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作者:
Mann O

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人促黄体激素绒毛膜促性腺激素受体(LHCGR)是一种G蛋白偶联受体,由人绒毛膜促性腺激素(HCG)和促黄体生成素(LH)激活,这两种促性腺激素在排卵和黄体维持中起重要作用。LHCGR主要在卵巢组织中表达,在卵巢组织中通过环腺苷单核苷酸(CAMP)、钙离子和细胞外信号调节激酶(ERK)信号引起功能反应。LHCGR也定位于人类子宫内膜,据称在蜕膜化和着床过程中发挥作用。然而,这些观察是有争议的。在这项研究中,在整个周期子宫内膜组织和培养的人子宫内膜间质细胞(EnSC)的批量RNA测序数据中没有检测到编码LHCGR的转录本。然而,对单细胞RNA测序数据的分析显示了细胞间转录的异质性,并发现了一小部分基质细胞具有可识别的LHCGR转录本。在表达重组LHCGR的HEK-293细胞中,hCG和LH都能激发野生型HEK-293细胞所没有的cAMP、Ca~(2+)和ERK信号。然而,在原代EnSC培养中,这些反应都没有被概括。此外,EnSC的增殖、存活和蜕膜转化对hCG和LH都是无效的,无论用什么方法诱导分化。尽管我们质疑LHCGR在人类子宫内膜功能活跃水平表达的断言,但表达LHCGR转录本的EnSC的一个离散亚群的发现可能合理地解释了文献中相互矛盾的证据。
The human luteinising hormone chorionic gonadotropin receptor (LHCGR) is a G-protein coupled receptor activated by both human chorionic gonadotropin (hCG) and luteinizing hormone (LH), two structurally related gonadotropins with essential roles in ovulation and maintenance of the corpus luteum. LHCGR expression predominates in ovarian tissues where it elicits functional responses through cyclic adenosine mononucleotide (cAMP), Ca2+and extracellular signal-regulated kinase (ERK) signalling. LHCGR has also been localized to the human endometrium, with purported roles in decidualization and implantation. However, these observations are contentious. In this investigation, transcripts encodingLHCGRwere undetectable in bulk RNA sequencing datasets from whole cycling endometrial tissue and cultured human endometrial stromal cells (EnSC). However, analysis of single-cell RNA sequencing data revealed cell-to-cell transcriptional heterogeneity and identified a small subpopulation of stromal cells with discernibleLHCGRtranscripts. In HEK-293 cells expressing recombinant LHCGR, both hCG and LH elicited robust cAMP, Ca2+and ERK signals that were absent in wild type HEK-293 cells. However, none of these responses were recapitulated in primary EnSC cultures. In addition, proliferation, viability and decidual transformation of EnSC were refractory to both hCG and LH, irrespective of treatment to induce differentiation. Although we challenge the assertion that LHCGR is expressed at a functionally active level in the human endometrium, the discovery of a discrete subpopulation of EnSC that expressLHCGRtranscripts may plausibly account for the conflicting evidence in the literature.
早产和足月分娩中的人子宫肌层绒毛膜促性腺激素/黄体生成素受体。
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