Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro.
Di-2-ethylhexyl (DEHP) phthalate, one of the phthalates most widely distributed in our general environment, causes reproductive toxicity that is attributable to the action of its primary metabolite, mono(2-ethylhexyl) phthalate (MEHP). Here, we have investigated the effects of MEHP on steroidogenesis by primary cultures of immature and adult rat Leydig cells. In both cases MEHP (250muM) was found to inhibit stimulation of androgen production evoked by human chorionic gonadotropin (hCG). This was associated with decreased expression of steroidogenic acute regulatory (StAR) protein and reduced transport of cholesterol into mitochondria but no detectable adverse effect on steroidogenic enzymes. Moreover, upon exposure to MEHP alone, 5alpha-reductase activity was decreased in immature, but not in adult Leydig cells. All together, our findings demonstrate that MEHP exerts suppressive effects on hCG-activated steroidogenesis in primary cultures of immature and adult rat Leydig cells and suppresses 5alpha-reductase activity in immature and not of adult rat cells. This may partly explain the anti-androgenic effects of DEHP in vivo and indicate a higher susceptibility in younger subjects.
Svechnikov
Konstantin
K
Department of Woman and Child Health, Pediatric Endocrinology Unit, Q2:08, Karolinska Institute & University Hospital, SE-17176 Stockholm, Sweden. konstantin.svechnikov@ki.se
Svechnikova
Irina
I
Söder
Olle
O
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D015113:Androstane-3,17-diol / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010968:Plasticizers / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D006063:Chorionic Gonadotropin; D010750:Phosphoproteins; D010968:Plasticizers; D000098682:Steroidogenic Acute Regulatory Protein; D015113:Androstane-3,17-diol; D013739:Testosterone; D002784:Cholesterol; D004051:Diethylhexyl Phthalate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C016599:mono-(2-ethylhexyl)phthalate