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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gunnarsson, David Leffler, Per Ekwurtzel, Emelie Martinsson, Gunilla Liu, Kui Selstam, Gunnar |
| Description | Country affiliation: Sweden Author Affiliation: Gunnarsson D ( Department of Molecular Biology, Umeå University, S-901 87 Umeå, Sweden. gunnar.selstam@molbiol.umu.se) |
| Abstract | Phthalates are widely used as plasticizers in a number of daily-life products. 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 (25-100 microM) 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 (10-100 microM) 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-pituitary-gonadal axis. |
| File Format | HTM / HTML |
| ISSN | 14701626 |
| e-ISSN | 17417899 |
| Journal | Reproduction |
| Issue Number | 5 |
| Volume Number | 135 |
| Language | English |
| Publisher | BioScientifica |
| Publisher Date | 2008-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Reproductive Medicine Diethylhexyl Phthalate Adverse Effects Granulosa Cells Metabolism Leydig Cells Plasticizers Progesterone Biosynthesis Testosterone Aminoglutethimide Pharmacology Animals Blotting, Western Cell Line, Tumor Dose-response Relationship, Drug Enzyme Inhibitors Gonads Drug Effects Hydroxymethylglutaryl Coa Reductases Lipase Mice Phosphoproteins Reverse Transcriptase Polymerase Chain Reaction Stimulation, Chemical Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Embryology Endocrinology Reproductive Medicine Obstetrics and Gynecology |
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