Mann, O. N., Kong, C.-S., Lucas, E. S., Brosens, J. J., Hanyaloglu, A. C. and Brighton, P. J. (2022) Expression and function of the luteinizing hormone choriogonadotropin receptor in human endometrial stromal cells. Scientific Reports, 12 (1). 8624. doi:10.1038/s41598-022-12495-9 ISSN 2045-2322.

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Abstract

The human luteinising hormone choriogonadotropin 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 expression has also been localized to the human endometrium, with purported roles in decidualization and implantation. However, these observations are contentious. In this investigation, transcripts encoding LHCGR were 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 we identified a small subpopulation of stromal cells with detectable LHCGR transcripts. 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 express LHCGR transcripts may plausibly account for the conflicting evidence in the literature.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Chorionic gonadotropins, Chorionic gonadotropins -- Receptors, Luteinizing hormone , Luteinizing hormone -- Receptors, Hormone receptors, Endometrium -- Physiology, Cell receptors
Journal or Publication Title:	Scientific Reports
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Official Date:	21 May 2022
Dates:	Date Event 21 May 2022 Published 3 May 2022 Accepted 14 January 2022 Submitted
Volume:	12
Number:	1
Number of Pages:	15
Article Number:	8624
DOI:	10.1038/s41598-022-12495-9
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 June 2022
Date of first compliant Open Access:	29 June 2022
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID BB/S001565/1 UK Research and Innovation http://dx.doi.org/10.13039/100014013 212233/Z/18/Z Wellcome Trust http://dx.doi.org/10.13039/100010269 UNSPECIFIED Tommy’s National Miscarriage Research Centre https://www.tommys.org/

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