Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells
Abstract Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals. In this study, immunolocalization assay showed th...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-03-01
|
Series: | Cellular & Molecular Biology Letters |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s11658-019-0147-z |
id |
doaj-4234e15f016a4ad49f61e5fc0ae1d21f |
---|---|
record_format |
Article |
spelling |
doaj-4234e15f016a4ad49f61e5fc0ae1d21f2021-04-02T14:12:28ZengBMCCellular & Molecular Biology Letters1425-81531689-13922019-03-0124111410.1186/s11658-019-0147-zMelatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cellsYuan Gao0Xiaochun Wu1Shuqin Zhao2Yujun Zhang3Hailong Ma4Zhen Yang5Wanghao Yang6Chen Zhao7Li Wang8Quanwei Zhang9College of Life Science and Technology, Gansu Agricultural UniversityCollege of Veterinary Medicine, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityCollege of Life Science and Technology, Gansu Agricultural UniversityAbstract Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals. In this study, immunolocalization assay showed that MT1 and MT2 are highly expressed in Leydig cell membrane. To understand the biological function of melatonin receptors in hCG-induced testosterone synthesis, we generated melatonin receptor knockdown cells using specific siRNA and performed testosterone detection after hCG treatment. We found that knockdown of melatonin receptors, especially MTNR1A, led to an obvious decrease (> 60%) of testosterone level. Our further study revealed that knockdown of melatonin receptors repressed expression, at both the mRNA level and the protein level, of key steroidogenic genes, such as p450scc, p450c17 and StAR, which are essential for testosterone synthesis. hCG triggered endoplasmic reticulum (ER) stress to regulate steroidogenic genes’ expression and apoptosis. To further investigate the potential roles of melatonin receptors in hCG-induced regulation of ER stress and apoptosis, we examined expression of some crucial ER stress markers, including Grp78, Chop, ATF4, Xbp1, and IRE1. We found that inhibition of melatonin receptors increased hCG-induced expression of Grp78, Chop and ATF4, but not Xbp1 and IRE1, suggesting that hCG may modulate IRE1 signaling pathways in a melatonin receptor-dependent manner. In addition, our further data showed that knockdown of MTNR1A and MTNR1B promoted hCG-induced expression of apoptosis markers, including p53, caspase-3 and Bcl-2. These results suggested that the melatonin receptors MTNR1A and MTNR1B are essential to repress hCG-induced ER stress and cell apoptosis. Our studies demonstrated that the mammalian melatonin receptors MT1 and MT2 are involved in testosterone synthesis via mediating multiple cell pathways.http://link.springer.com/article/10.1186/s11658-019-0147-zMelatonin receptorTestosteroneER stressApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan Gao Xiaochun Wu Shuqin Zhao Yujun Zhang Hailong Ma Zhen Yang Wanghao Yang Chen Zhao Li Wang Quanwei Zhang |
spellingShingle |
Yuan Gao Xiaochun Wu Shuqin Zhao Yujun Zhang Hailong Ma Zhen Yang Wanghao Yang Chen Zhao Li Wang Quanwei Zhang Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells Cellular & Molecular Biology Letters Melatonin receptor Testosterone ER stress Apoptosis |
author_facet |
Yuan Gao Xiaochun Wu Shuqin Zhao Yujun Zhang Hailong Ma Zhen Yang Wanghao Yang Chen Zhao Li Wang Quanwei Zhang |
author_sort |
Yuan Gao |
title |
Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells |
title_short |
Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells |
title_full |
Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells |
title_fullStr |
Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells |
title_full_unstemmed |
Melatonin receptor depletion suppressed hCG-induced testosterone expression in mouse Leydig cells |
title_sort |
melatonin receptor depletion suppressed hcg-induced testosterone expression in mouse leydig cells |
publisher |
BMC |
series |
Cellular & Molecular Biology Letters |
issn |
1425-8153 1689-1392 |
publishDate |
2019-03-01 |
description |
Abstract Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals. In this study, immunolocalization assay showed that MT1 and MT2 are highly expressed in Leydig cell membrane. To understand the biological function of melatonin receptors in hCG-induced testosterone synthesis, we generated melatonin receptor knockdown cells using specific siRNA and performed testosterone detection after hCG treatment. We found that knockdown of melatonin receptors, especially MTNR1A, led to an obvious decrease (> 60%) of testosterone level. Our further study revealed that knockdown of melatonin receptors repressed expression, at both the mRNA level and the protein level, of key steroidogenic genes, such as p450scc, p450c17 and StAR, which are essential for testosterone synthesis. hCG triggered endoplasmic reticulum (ER) stress to regulate steroidogenic genes’ expression and apoptosis. To further investigate the potential roles of melatonin receptors in hCG-induced regulation of ER stress and apoptosis, we examined expression of some crucial ER stress markers, including Grp78, Chop, ATF4, Xbp1, and IRE1. We found that inhibition of melatonin receptors increased hCG-induced expression of Grp78, Chop and ATF4, but not Xbp1 and IRE1, suggesting that hCG may modulate IRE1 signaling pathways in a melatonin receptor-dependent manner. In addition, our further data showed that knockdown of MTNR1A and MTNR1B promoted hCG-induced expression of apoptosis markers, including p53, caspase-3 and Bcl-2. These results suggested that the melatonin receptors MTNR1A and MTNR1B are essential to repress hCG-induced ER stress and cell apoptosis. Our studies demonstrated that the mammalian melatonin receptors MT1 and MT2 are involved in testosterone synthesis via mediating multiple cell pathways. |
topic |
Melatonin receptor Testosterone ER stress Apoptosis |
url |
http://link.springer.com/article/10.1186/s11658-019-0147-z |
work_keys_str_mv |
AT yuangao melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT xiaochunwu melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT shuqinzhao melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT yujunzhang melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT hailongma melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT zhenyang melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT wanghaoyang melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT chenzhao melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT liwang melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells AT quanweizhang melatoninreceptordepletionsuppressedhcginducedtestosteroneexpressioninmouseleydigcells |
_version_ |
1721562787974479872 |