HCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in leydig cells of the testis

Cited 52 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorS J Park-
dc.contributor.authorT S Kim-
dc.contributor.authorC K Park-
dc.contributor.authorS H Lee-
dc.contributor.authorJ M Kim-
dc.contributor.authorKyu-Sun Lee-
dc.contributor.authorI K Lee-
dc.contributor.authorJ W Park-
dc.contributor.authorM A Lawson-
dc.contributor.authorD S Lee-
dc.date.accessioned2017-04-19T09:36:59Z-
dc.date.available2017-04-19T09:36:59Z-
dc.date.issued2013-
dc.identifier.issn09525041-
dc.identifier.uri10.1530/JME-12-0195ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11225-
dc.description.abstractEndoplasmic reticulum (ER) stress generally occurs in secretory cell types. It has been reported that Leydig cells, which produce testosterone in response to human chorionic gonadotropin (hCG), express key steroidogenic enzymes for the regulation of testosterone synthesis. In this study, we analyzed whether hCG induces ER stress via three unfolded protein response (UPR) pathways in mouse Leydig tumor (mLTC-1) cells and the testis. Treatment with hCG induced ER stress in mLTC-1 cells via the ATF6, IRE1a/XBP1, and eIF2a/GADD34/ATF4 UPR pathways, and transient expression of 50 kDa protein activating transcription factor 6 (p50ATF6) reduced the expression level of steroidogenic 3b-hydroxy-steroid dehydrogenase O5-O4-isomerase (3b-HSD) enzyme. In an in vivo model, high-level hCG treatment induced expression of p50ATF6 while that of steroidogenic enzymes, especially 3b-HSD, 17a-hydroxylase/C17-20 lyase (CYP17), and 17b-hydrozysteroid dehydrogenase (17b-HSD), was reduced. Expression levels of steroidogenic enzymes were restored by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Furthermore, lentivirus-mediated transient expression of p50ATF6 reduced the expression level of 3b-HSD in the testis. Protein expression levels of phospho-JNK, CHOP, and cleaved caspases-12 and -3 as markers of ER stress-mediated apoptosis markedly increased in response to high-level hCG treatment in mLTC-1 cells and the testis. Based on transmission electron microscopy and H&E staining of the testis, it was shown that abnormal ER morphology and destruction of testicular histology induced by high-level hCG treatment were reversed by the addition of TUDCA. These findings suggest that hCG-induced ER stress plays important roles in steroidogenic enzyme expression via modulation of the ATF6 pathway as well as ER stress-mediated apoptosis in Leydig cells.-
dc.publisherBioscientifica Ltd-
dc.titleHCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in leydig cells of the testis-
dc.title.alternativeHCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in leydig cells of the testis-
dc.typeArticle-
dc.citation.titleJournal of Molecular Endocrinology-
dc.citation.number2-
dc.citation.endPage166-
dc.citation.startPage151-
dc.citation.volume50-
dc.contributor.affiliatedAuthorKyu-Sun Lee-
dc.contributor.alternativeName박선지-
dc.contributor.alternativeName김태신-
dc.contributor.alternativeName박춘근-
dc.contributor.alternativeName이상희-
dc.contributor.alternativeName김진만-
dc.contributor.alternativeName이규선-
dc.contributor.alternativeName이인규-
dc.contributor.alternativeName박진우-
dc.contributor.alternativeNameLawson-
dc.contributor.alternativeName이동석-
dc.identifier.bibliographicCitationJournal of Molecular Endocrinology, vol. 50, no. 2, pp. 151-166-
dc.identifier.doi10.1530/JME-12-0195-
dc.subject.keywordActivating transaction factor 6-
dc.subject.keywordER stress-
dc.subject.keywordLeydig cells-
dc.subject.keywordSteroidogenic enzyme expression-
dc.subject.keywordTestosterone-
dc.subject.localActivating transaction factor 6-
dc.subject.localER stress-
dc.subject.localLeydig cells-
dc.subject.localSteroidogenic enzyme expression-
dc.subject.localTestosterone-
dc.description.journalClassY-
Appears in Collections:
Division of Biomaterials Research > Bionanotechnology Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.