title: Mono-2-ethylhexyl phthalate stimulates androgen production but suppresses mitochondrial function in mouse leydig cells with different steroidogenic potential.
abstract: Numerous studies have reported on testicular toxicity of phthalates in different experimental paradigms and showed that Leydig cells (LCs) were one of the main targets of phthalate actions. Adverse effects of phthalates on LCs steroidogenesis have been attributed to their metabolites, monophthalates. This study focuses on investigation whether LCs responsiveness to monophthalates action is associated with their potential to produce androgens. We found that of 3 monophthalates investigated [ie, mono-2-ethylhexyl phthalate (MEHP), mono-n-butyl phthalate, and mono-n-benzyl phthalate] only MEHP caused biological effects on the mouse LCs function. This monophthalate stimulated basal steroidogenesis associated with upregulation of StAR protein expression with no effect on hCG-stimulated androgen production by LCs from CBA/Lac and C57BL/6j mouse genotypes were observed. Further, MEHP attenuated ATP production and increased superoxide generation by both phenotypes of mouse LCs that indicated on mitochondrial dysfunction induced by the monophthalate. All together, our data indicate that MEHP-mediated stimulation of steroidogenesis and perturbation in mitochondrial function are not associated with the capacity of the LCs to synthesize androgens. We suggest that this effect of MEHP observed in LCs of rodent origin needs to be taken into consideration in analysis of earlier start of puberty in boys and may highlight a possible influence of phthalates on reproductive health in males.
authors: Department of Woman and Child Health, Pediatric Endocrinology Unit Q2:08, Karolinska Institute and University Hospital, Astrid Lindgren Children's Hospital, SE-17176 Stockholm, Sweden konstantin.svechnikov@ki.se.
authors: Iuliia
authors: I
authors: Savchuk
authors: Department of Woman and Child Health, Pediatric Endocrinology Unit Q2:08, Karolinska Institute and University Hospital, Astrid Lindgren Children's Hospital, SE-17176 Stockholm, Sweden.
authors: Olle
authors: O
authors: Söder
authors: Department of Woman and Child Health, Pediatric Endocrinology Unit Q2:08, Karolinska Institute and University Hospital, Astrid Lindgren Children's Hospital, SE-17176 Stockholm, Sweden konstantin.svechnikov@ki.se.
authors: Konstantin
authors: K
authors: Svechnikov
mesh_terms: D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000728:Androgens; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate
keywords: Leydig cells; MEHP; StAR; mitochondria; monophthalates; mouse genotypes; steroidogenesis