Journal Article

BLTK1 Murine Leydig Cells: A Novel Steroidogenic Model for Evaluating the Effects of Reproductive and Developmental Toxicants

Agnes L. Forgacs, Qi Ding, Rosemary G. Jaremba, Ilpo T. Huhtaniemi, Nafis A. Rahman and Timothy R. Zacharewski

in Toxicological Sciences

Volume 127, issue 2, pages 391-402
Published in print June 2012 | ISSN: 1096-6080
Published online March 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs121
BLTK1 Murine Leydig Cells: A Novel Steroidogenic Model for Evaluating the Effects of Reproductive and Developmental Toxicants

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Leydig cells are the primary site of androgen biosynthesis in males. Several environmental toxicants target steroidogenesis resulting in both developmental and reproductive effects including testicular dysgenesis syndrome. The aim of this study was to evaluate the effect of several structurally diverse endocrine disrupting compounds (EDCs) on steroidogenesis in a novel BLTK1 murine Leydig cell model. We demonstrate that BLTK1 cells possess a fully functional steroidogenic pathway that produces low basal levels of testosterone (T) and express all the necessary steroidogenic enzymes including Star, Cyp11a1, Cyp17a1, Hsd3b1, Hsd17b3, and Srd5a1. Recombinant human chorionic gonadotropin (rhCG) and forskolin (FSK) elicited concentration- and time-dependent induction of 3′,5′-cyclic adenosine monophosphate, progesterone (P), and T, as well as the differential expression of Star, Hsd3b6, Hsd17b3, and Srd5a1 messenger RNA levels. The evaluation of several structurally diverse male reproductive toxicants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), atrazine, prochloraz, triclosan, monoethylhexyl phthalate (MEHP), glyphosate, and RDX in BLTK1 cells suggests different modes of action perturb steroidogenesis. For example, prochloraz and triclosan antifungals reduced rhCG induction of T, consistent with published in vivo data but did not alter basal T levels. In contrast, atrazine and MEHP elicited modest induction of basal T but antagonized rhCG-mediated induction of T levels, whereas TCDD, glyphosate, and RDX had no effect on basal or rhCG induction of T in BLTK1 cells. These results suggest that BLTK1 cells maintain rhCG-inducible steroidogenesis and are a viable in vitro Leydig cell model to evaluate the effects of EDCs on steroidogenesis. This model can also be used to elucidate the different mechanisms underlying toxicant-mediated disruption of steroidogenesis.

Keywords: steroidogenesis; Leydig cells; endocrine disruptors; endocrine toxicology

Journal Article.  6521 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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