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In this study, we investigated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used plasticizer di-(2-ethylhexyl) phthalate (DEHP), on gonadal steroidogenesis in vitro. MEHP (25\u2013100\u200a\u03bcM) stimulated basal steroid synthesis in a concentration-dependent manner in immortalized mouse Leydig tumor cells (MLTC-1). The stimulatory effect was also detected in KK-1 granulosa tumor cells. MEHP exposure did not influence cAMP or StAR protein levels and induced a gene expression profile of key steroidogenic proteins different from the one induced by human chorionic gonadotropin (hCG). Simultaneous treatment with MEHP and a p450scc inhibitor (aminoglutethimide) indicated that MEHP exerts its main stimulatory effect prior to pregnenolone formation. MEHP (10\u2013100\u200a\u03bcM) up-regulated hormone-sensitive lipase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, suggesting that MEHP increases the amount of cholesterol available for steroidogenesis. Our data suggest that MEHP, besides its known inhibitory effect on hCG action, can directly stimulate gonadal steroidogenesis in both sexes through a cAMP- and StAR-independent mechanism. The anti-steroidogenic effect of DEHP has been proposed to cause developmental disorders such as hypospadias and cryptorchidism, whereas a stimulation of steroid synthesis may prematurely initiate the onset of puberty and theoretically affect the hypothalamic\u2013pituitary\u2013gonadal axis.<\/jats:p>","DOI":"10.1530\/rep-07-0460","type":"journal-article","created":{"date-parts":[[2008,4,11]],"date-time":"2008-04-11T11:48:19Z","timestamp":1207914499000},"page":"693-703","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":74,"title":["Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes"],"prefix":"10.1093","volume":"135","author":[{"given":"David","family":"Gunnarsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Leffler","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Ume\u00e5 University, S-901 87 Ume\u00e5, Sweden 1Division of CBRN Defence and Security Swedish Defence Research Agency, Department of Threat Assessment, Cementv\u00e4gen 20, S-901 82 Ume\u00e5, Sweden 2Department of Medical Biochemistry and Biophysics Ume\u00e5 University, S-901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelie","family":"Ekwurtzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunilla","family":"Martinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Ume\u00e5 University, S-901 87 Ume\u00e5, Sweden 1Division of CBRN Defence and Security Swedish Defence Research Agency, Department of Threat Assessment, Cementv\u00e4gen 20, S-901 82 Ume\u00e5, Sweden 2Department of Medical Biochemistry and Biophysics Ume\u00e5 University, S-901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Selstam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,5,1]]},"reference":[{"key":"2026010713131716500_bib1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.mce.2005.11.047","article-title":"Phenotypic characterisation of mice with exaggerated and missing LH\/hCG action","volume":"260\u2013262","author":"Ahtiainen","year":"2007","journal-title":"Molecular and Cellular Endocrinology"},{"key":"2026010713131716500_bib2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1210\/mend-1-9-595","article-title":"Noncoordinate regulation of de novo synthesis of cytochrome P-450 cholesterol side-chain cleavage and cytochrome P-450 17 alpha-hydroxylase\/C17-20 lyase in mouse Leydig cell cultures: relation to steroid production","volume":"1","author":"Anakwe","year":"1987","journal-title":"Molecular Endocrinology"},{"key":"2026010713131716500_bib3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.tox.2006.08.020","article-title":"A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats","volume":"228","author":"Andrade","year":"2006","journal-title":"Toxicology"},{"key":"2026010713131716500_bib4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.beem.2005.09.004","article-title":"Testicular dysgenesis syndrome: possible role of endocrine disrupters","volume":"20","author":"Bay","year":"2006","journal-title":"Best Practice and Research. 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