Mechanism of bisphenol AF-induced progesterone inhibition in human chorionic gonadotrophin-stimulated mouse Leydig tumor cell line (mLTC-1) cells
| Autor: | Zhihao Jiao, Hejun Duan, Jiachen Shi, Yixing Feng, Bing Shao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male endocrine system medicine.medical_specialty Health Toxicology and Mutagenesis 010501 environmental sciences Management Monitoring Policy and Law Steroid biosynthesis Endocrine Disruptors Toxicology 01 natural sciences Chorionic Gonadotropin 03 medical and health sciences chemistry.chemical_compound Mice Phenols Internal medicine Cell Line Tumor medicine Cyclic AMP Animals Humans Cyclic adenosine monophosphate Scavenger receptor Benzhydryl Compounds IC50 Progesterone 0105 earth and related environmental sciences biology Cholesterol side-chain cleavage enzyme Steroidogenic acute regulatory protein Cytochrome P450 Leydig Cells General Medicine Progesterone secretion 030104 developmental biology Endocrinology chemistry biology.protein Leydig Cell Tumor |
| Zdroj: | Environmental toxicology. 33(6) |
| ISSN: | 1522-7278 |
| Popis: | Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male rats. However, the precise mechanisms related to the toxic effects of BPAF on reproduction remain poorly understood. In the present study, a mouse Leydig tumor cell line (mLTC-1) was used as a model to investigate the mechanism of steroidogenic inhibition and to identify the molecular target of BPAF. Levels of progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in cells exposed to BPAF were detected, and expression of key genes and proteins in steroid biosynthesis was assessed. The results showed that BPAF exposure decreased human chorionic gonadotrophin (hCG)-stimulated progesterone production in a dose-dependent manner. The 24-h IC50 (half maximal inhibitory concentration) value for BPAF regarding progesterone production was 70.2 µM. A dramatic decrease in cellular cAMP concentration was also observed. Furthermore, BPAF exposure inhibited expression of genes and proteins involved in cholesterol transport and progesterone biosynthesis. Conversely, the protein levels of steroidogenic acute regulatory protein (StAR) were not altered, and those of progesterone were still decreased upon 22R-hydroxycholesterol treatment of cells exposed to higher doses of BPAF. Together, these data indicate that BPAF exposure inhibits progesterone secretion in hCG-stimulated mLTC-1 cells by reducing expression of scavenger receptor class B type I (SR-B1) and cytochrome P450 (P450scc) due to the adverse effects of cAMP. However, StAR might not be the molecular target in this process. |
| Databáze: | OpenAIRE |
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