title: The inhibitory effects of lead on steroidogenesis in MA-10 mouse Leydig tumor cells.
abstract: Lead is an environmental and occupational pollutant. It has been reported that lead affects the male reproductive system in humans and animals. However, the cellular mechanism of the adverse effect of lead on Leydig cell steroidogenesis remains unknown. To clarify whether lead has a direct effect on Leydig cells and how lead affects Leydig cells, MA-10 cells, a mouse Leydig tumor cell line, were exploited in this study. Lead acetate significantly inhibited hCG- and dbcAMP-stimulated progesterone production in MA-10 cells at 2 h. Steroid production stimulated by hCG or dbcAMP were reduced by lead. The mechanism of lead in reducing MA-10 cell steroidogenesis was further investigated. The expression of Steroidogenic Acute Regulatory (StAR) protein and the activities of P450 side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzymes were detected. Cells were treated with dbcAMP, 22R-hydroxycholesterol or pregnenolone alone or in combination with lead acetate ranging from 10(-8) to 10(-5) M for 2 h. The expression of StAR protein stimulated by dbcAMP was suppressed by lead at about 50%. Progesterone productions treated with 22R-hydroxycholesterol or pregnenolone were reduced 30-40% in lead-treated MA-10 cells. These data suggest that lead directly inhibited steroidogenesis by decreasing StAR protein expression and the activities of P450scc and 3beta-HSD enzymes with a dose-response trend in MA-10 cells. Moreover, cadmium, a calcium channel blocker, abolished inhibitory effect of lead on MA-10 cell steroid production. This indicates that lead might act on calcium channel to regulate MA-10 cell steroidogenesis.
authors.affiliation: Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: M Y
authors.initials: MY
authors.lastname: Liu
authors.forename: H Y
authors.initials: HY
authors.lastname: Lai
authors.forename: B C
authors.initials: BC
authors.lastname: Yang
authors.forename: M L
authors.initials: ML
authors.lastname: Tsai
authors.forename: H Y
authors.initials: HY
authors.lastname: Yang
authors.forename: B M
authors.initials: BM
authors.lastname: Huang
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006888:Hydroxycholesterols / Q000494:pharmacology; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D007984:Leydig Cell Tumor; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D010750:Phosphoproteins / Q000096:biosynthesis*; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D009942:Organometallic Compounds; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D002104:Cadmium; C003585:22-hydroxycholesterol; D007854:Lead; D011374:Progesterone; D003994:Bucladesine; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; C008261:lead acetate