title: Effect of 2,2',4,4'-tetrahydroxybenzophenone (BP2) on steroidogenesis in testicular Leydig cells.
abstract: Endocrine disruptors (EDs) affect the function of animal reproductive systems. Recently, 2,2',4,4'-tetrahydroxybenzophenone (BP2), which is a component of UV protection products, was found to be an ED that interferes with the thyroid hormone (TH) axis. However, BP2 activity in the testis has not been well addressed. In this study, we have examined the effects of BP2 on steroidogenesis in testicular Leydig cells in connection with thyroid hormone signaling, which is known to play an important role in testicular development and function. Our study showed that BP2 affected the expression of steroidogenic enzyme genes in testicular Leydig cells, which is differentially regulated by thyroid hormone/thyroid hormone receptor (TR) signaling. In MA-10 Leydig cell line, TR/T3 signaling increased the expression of P450c17 and P450scc, while it decreased the expression of StAR and 3β-HSD. Interestingly, BP2 affected the expression of steroidogenic enzyme genes in a manner opposite to that of T3 signaling. BP2 downregulated the TRα/T3-activation of P450c17 and P450scc expression while enhancing the TRα/T3-repression of StAR and 3β-HSD expression. Transient transfection analyses with promoter-reporter constructs revealed that BP2 altered the expression of steroidogenic enzyme genes by affecting the cAMP and Nur77-activated promoter activity of P450c17, StAR, and 3β-HSD. Animal experiments with mice revealed that BP2 decreased the production of testosterone in the testis by affecting the expression of some steroidogenic enzyme genes in vivo. Together, these findings elucidate a molecular mechanism of BP2 action underlying testicular steroidogenesis and also suggest that BP2 acts, in part, as a thyroid antagonist that affects steroidogenesis in the testis.
authors: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Yeawon
authors: Y
authors: Kim
authors: Jae Chun
authors: JC
authors: Ryu
authors: Hueng-Sik
authors: HS
authors: Choi
authors: Keesook
authors: K
authors: Lee
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000633:toxicity*; D002460:Cell Line; D052244:Endocrine Disruptors / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D014162:Transfection; D014284:Triiodothyronine / Q000187:drug effects / Q000378:metabolism
chemical_list: D001577:Benzophenones; D052244:Endocrine Disruptors; D011988:Receptors, Thyroid Hormone; D013256:Steroids; D014284:Triiodothyronine; D013739:Testosterone; C035476:2,2',4,4'-tetrahydroxybenzophenone