Cargando…

Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis

An association between endometriosis and luteinized unruptured follicle syndrome (LUFs) has long been identified. Although inactivating mutation of luteinizing hormone/choriogonadotropin receptor (LHGCR) results in LUFs, whether LHCGR contributes to promoting LUFs in endometriosis remains elusive. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Geng, Ting, Sun, Yifan, Cheng, Lin, Cao, Yuming, Zhang, Ming, Hong, Zhidan, Ma, Ling, Zhang, Yuanzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114297/
https://www.ncbi.nlm.nih.gov/pubmed/35600595
http://dx.doi.org/10.3389/fendo.2022.853563
_version_ 1784709739865702400
author Geng, Ting
Sun, Yifan
Cheng, Lin
Cao, Yuming
Zhang, Ming
Hong, Zhidan
Ma, Ling
Zhang, Yuanzhen
author_facet Geng, Ting
Sun, Yifan
Cheng, Lin
Cao, Yuming
Zhang, Ming
Hong, Zhidan
Ma, Ling
Zhang, Yuanzhen
author_sort Geng, Ting
collection PubMed
description An association between endometriosis and luteinized unruptured follicle syndrome (LUFs) has long been identified. Although inactivating mutation of luteinizing hormone/choriogonadotropin receptor (LHGCR) results in LUFs, whether LHCGR contributes to promoting LUFs in endometriosis remains elusive. To investigate the effect of LHCGR signaling in the development of endometriosis-associated LUFs and dissect the underlying mechanism in vivo mouse endometriosis model was established to measure the effect on ovarian folliculogenesis. In vitro cultures of primary human GCs collected from patients undergoing in vitro fertilization were performed and treated with human chorionic gonadotropin (hCG), dibutyryl cyclic-AMP (db-cAMP), LHCGR or CCAAT/enhancer binding protein-α (C/EBPα) small interfering RNA to identify the potential mechanisms. KGN cell line was used to investigate the mechanistic features of transcriptional regulation. Results showed an increased incidence of LUFs was observed in mice with endometriosis. The expression of LHCGR was decreased in the GCs of endometriosis mice. In in vitro cell models, LHCGR signaling increased the expression of C/EBPα and cyclooxygenase-2(COX-2), while inhibiting C/EBPα mitigated the induced COX-2 expression. Mechanically, C/EBPα bounded to the promoter region of COX-2 and increased the transcriptional activity under the stimulation of hCG or db-cAMP. Taken together, this study demonstrated that the LHCGR signaling was reduced in GCs of endometriosis and resulted in a decrease in gonadotropin-induced COX-2 expression. Our study might provide new insights into the dysfunction of GCs in endometriosis.
format Online
Article
Text
id pubmed-9114297
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91142972022-05-19 Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis Geng, Ting Sun, Yifan Cheng, Lin Cao, Yuming Zhang, Ming Hong, Zhidan Ma, Ling Zhang, Yuanzhen Front Endocrinol (Lausanne) Endocrinology An association between endometriosis and luteinized unruptured follicle syndrome (LUFs) has long been identified. Although inactivating mutation of luteinizing hormone/choriogonadotropin receptor (LHGCR) results in LUFs, whether LHCGR contributes to promoting LUFs in endometriosis remains elusive. To investigate the effect of LHCGR signaling in the development of endometriosis-associated LUFs and dissect the underlying mechanism in vivo mouse endometriosis model was established to measure the effect on ovarian folliculogenesis. In vitro cultures of primary human GCs collected from patients undergoing in vitro fertilization were performed and treated with human chorionic gonadotropin (hCG), dibutyryl cyclic-AMP (db-cAMP), LHCGR or CCAAT/enhancer binding protein-α (C/EBPα) small interfering RNA to identify the potential mechanisms. KGN cell line was used to investigate the mechanistic features of transcriptional regulation. Results showed an increased incidence of LUFs was observed in mice with endometriosis. The expression of LHCGR was decreased in the GCs of endometriosis mice. In in vitro cell models, LHCGR signaling increased the expression of C/EBPα and cyclooxygenase-2(COX-2), while inhibiting C/EBPα mitigated the induced COX-2 expression. Mechanically, C/EBPα bounded to the promoter region of COX-2 and increased the transcriptional activity under the stimulation of hCG or db-cAMP. Taken together, this study demonstrated that the LHCGR signaling was reduced in GCs of endometriosis and resulted in a decrease in gonadotropin-induced COX-2 expression. Our study might provide new insights into the dysfunction of GCs in endometriosis. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9114297/ /pubmed/35600595 http://dx.doi.org/10.3389/fendo.2022.853563 Text en Copyright © 2022 Geng, Sun, Cheng, Cao, Zhang, Hong, Ma and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Geng, Ting
Sun, Yifan
Cheng, Lin
Cao, Yuming
Zhang, Ming
Hong, Zhidan
Ma, Ling
Zhang, Yuanzhen
Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title_full Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title_fullStr Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title_full_unstemmed Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title_short Downregulation of LHCGR Attenuates COX-2 Expression and Induces Luteinized Unruptured Follicle Syndrome in Endometriosis
title_sort downregulation of lhcgr attenuates cox-2 expression and induces luteinized unruptured follicle syndrome in endometriosis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114297/
https://www.ncbi.nlm.nih.gov/pubmed/35600595
http://dx.doi.org/10.3389/fendo.2022.853563
work_keys_str_mv AT gengting downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT sunyifan downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT chenglin downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT caoyuming downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT zhangming downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT hongzhidan downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT maling downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis
AT zhangyuanzhen downregulationoflhcgrattenuatescox2expressionandinducesluteinizedunrupturedfolliclesyndromeinendometriosis