Insulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular leydig cells

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dc.contributor.authorS W Ahn-
dc.contributor.authorGil Tae Gang-
dc.contributor.authorY D Kim-
dc.contributor.authorR S Ahn-
dc.contributor.authorR A Harris-
dc.contributor.authorChul Ho Lee-
dc.contributor.authorH S Choi-
dc.date.accessioned2017-04-19T09:40:15Z-
dc.date.available2017-04-19T09:40:15Z-
dc.date.issued2013-
dc.identifier.issn0021-9258-
dc.identifier.uri10.1074/jbc.M113.451773ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11346-
dc.description.abstractTestosterone level is low in insulin-resistant type 2 diabetes. Whether this is due to negative effects of high level of insulin on the testes caused by insulin resistance has not been studied in detail. In this study, we found that insulin directly binds to insulin receptors in Leydig cell membranes and activates phosphoinsulin receptor-β (phospho-IR-β), phospho-IRS1, and phospho-AKT, leading to up-regulation of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) gene expression in the MA-10 mouse Leydig cell line. Insulin also inhibits cAMP-induced and liver receptor homolog-1 (LRH-1)-induced steroidogenic enzyme gene expression and steroidogenesis. In contrast, knockdown of DAX-1 reversed insulin-mediated inhibition of steroidogenesis. Whether insulin directly represses steroidogenesis through regulation of steroidogenic enzyme gene expression was assessed in insulin-injected mouse models and high fat diet-induced obesity. In insulin-injected mouse models, insulin receptor signal pathway was activated and subsequently inhibited steroidogenesis via induction of DAX-1 without significant change of luteinizing hormone or FSH levels. Likewise, the levels of steroidogenic enzyme gene expression and steroidogenesis were low, but interestingly, the level of DAX-1 was high in the testes of high fat diet-fed mice. These results represent a novel regulatory mechanism of steroidogenesis in Leydig cells. Insulin-mediated induction of DAX-1 in Leydig cells of testis may be a key regulatory step of serum sex hormone level in insulin-resistant states.-
dc.publisherAmer Soc Biochemistry Molecular Biology Inc-
dc.titleInsulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular leydig cells-
dc.title.alternativeInsulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular leydig cells-
dc.typeArticle-
dc.citation.titleJournal of Biological Chemistry-
dc.citation.number22-
dc.citation.endPage15946-
dc.citation.startPage15937-
dc.citation.volume288-
dc.contributor.affiliatedAuthorGil Tae Gang-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.alternativeName안승원-
dc.contributor.alternativeName강길태-
dc.contributor.alternativeName김용득-
dc.contributor.alternativeName안윤섭-
dc.contributor.alternativeNameHarris-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName최흥식-
dc.identifier.bibliographicCitationJournal of Biological Chemistry, vol. 288, no. 22, pp. 15937-15946-
dc.identifier.doi10.1074/jbc.M113.451773-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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