BLTK1 Murine Leydig Cells: A Novel Steroidogenic Model for Evaluating the Effects of Reproductive and Developmental Toxicants
Forgacs, AL; Ding, Q; Jaremba, RG; Huhtaniemi, IT; Rahman, NA; Zacharewski, TR
HERO ID
1065711
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1065711 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | BLTK1 Murine Leydig Cells: A Novel Steroidogenic Model for Evaluating the Effects of Reproductive and Developmental Toxicants |
| Authors | Forgacs, AL; Ding, Q; Jaremba, RG; Huhtaniemi, IT; Rahman, NA; Zacharewski, TR |
| Journal | Toxicological Sciences |
| Volume | 127 |
| Issue | 2 |
| Page Numbers | 391-402 |
| Abstract | 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 (EDC) 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 cAMP, progesterone (P) and T, as well as the differential expression of Star, Hsd3b6, Hsd17b3 and Srd5a1 mRNA 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 suggest different modes of action perturb steroidogenesis. For example, prochloraz and triclosan anti-fungals 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 steroidogeneis. |
| Doi | 10.1093/toxsci/kfs121 |
| Pmid | 22461451 |
| Wosid | WOS:000304198400008 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000304198400008 |
| Is Public | Yes |
| Language Text | English |
| Keyword | steroidogenesis; Leydig cells; endocrine disruptors; endocrine toxicology |
| Is Qa | No |