{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:35:13Z","timestamp":1790328913285,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T00:00:00Z","timestamp":1524182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Tehran University of Medical Sciences and Health Services, Tehran, Iran","award":["93-03-30-26837"],"award-info":[{"award-number":["93-03-30-26837"]}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in reproductive\u2010aged women. Hormonal abnormality caused by steroidogenesis disturbances appears to be the main culprit of the clinical picture in PCOS. Vitamin D3 could regulate steroidogenesis in granulosa cells, but the mechanism of action of vitamin D3 on steroidogenesis remains unknown. AMP\u2010activated protein kinase (AMPK) has a modulating role in steroid hormone production. We investigated the effect of vitamin D3 on steroidogenesis in cultured granulosa cells of dehydroepiandrosterone\u2010induced PCOS mice and studied the involvement of AMPK signalling pathway in the current process. Immunoblotting assay showed that vitamin D3 could increase phosphorylation of AMPK alpha and acetyl\u2010CoA carboxylase, main substrate of AMPK. Vitamin D3 and 5\u2010aminoimidazole\u20104\u2010carboxamide\u20101\u2010\u03b2\u2010D\u2010riboside or Aicar (AMPK activator) not only reduced gene expression of steroidogenic enzymes (<jats:italic>P450scc<\/jats:italic> or <jats:italic>Cyp11a1<\/jats:italic>, <jats:italic>StAR<\/jats:italic>, <jats:italic>Cyp19a1<\/jats:italic> and <jats:italic>3B\u2010HSD<\/jats:italic>), but also reduced production of progesterone and 17B\u2010estradiol assessed by radioimmunoassay. Pretreatment with compound C (AMPK inhibitor) decreased APMK phosphorylation and eliminated the effects of vitamin D3 and Aicar on steroidogenic enzymes expression and estradiol and progesterone production. This study showed that vitamin D3 has the main role in regulating of steroidogenesis in granulosa cells of mouse polycystic ovary through activation of the AMPK signalling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance of the Study<\/jats:title><jats:p>Polycystic ovarian syndrome (PCOS) is an endocrine disorder of women in reproductive age. This disorder is partly related to disruption in steroidogenesis pathway and dysregulation of estradiol and progesterone production in granulosa cells of polycystic ovaries. Previously, we have shown that vitamin D3 could modulate steroidogenesis pathway in PCOS granulosa cells. In this study, we investigate the molecular mechanism of vitamin D3 in regulation of steroidogenesis pathway. We have shown that vitamin D3 has a modulating role in steroidogenesis pathway of granulosa cells by regulation of AMP\u2010activated protein kinase (AMPK) as an underlying molecular mechanism in mouse polycystic ovary.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3330","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T06:45:58Z","timestamp":1524206758000},"page":"183-193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Vitamin D3 regulates steroidogenesis in granulosa cells through AMP\u2010activated protein kinase (AMPK) activation in a mouse model of polycystic ovary syndrome"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-696X","authenticated-orcid":false,"given":"Shabnam","family":"Bakhshalizadeh","sequence":"first","affiliation":[{"name":"Department of Anatomical Sciences, School of Medicine Zanjan University of Medical Sciences  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