Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 25; no. 4; pp. 485 - 490
• Main Authors: Svechnikov, Konstantin, Svechnikova, Irina, Söder, Olle
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2008; Elsevier
• Subjects: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism; Androstane-3,17-diol - metabolism; Animals; Biological and medical sciences; Cells, Cultured; Cholesterol - metabolism; Chorionic Gonadotropin - pharmacology; Diethylhexyl Phthalate - analogs & derivatives; Diethylhexyl Phthalate - toxicity; Embryology: invertebrates and vertebrates. Teratology; Fundamental and applied biological sciences. Psychology; Leydig cells; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Medical sciences; MEHP; Phosphoproteins - metabolism; Plasticizers - toxicity; Rats; Rats, Sprague-Dawley; StAR; Steroidogenesis; Teratology. Teratogens; Testosterone - metabolism; Toxicology; Steroidogenesis; MEHP; StAR; Leydig cells; Rat; Rodentia; Phthalate; Testicle; Male genital system; In vitro; Leydig cell; Vertebrata; Mammalia; Adult animal; Leydig cells,MEHP,Steroidogenesis,StAR; Immaturity
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2008.05.057

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 (250 μM) 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, 5α-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 5α-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.