Concentration dependency in lead-inhibited steroidogenesis in MA-10 mouse Leydig tumor cells.
Lead acetate (Pb) decreases the expression of steroidogenic acute regulatory (StAR) protein and the enzymatic activities of cytochrome P-450 side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in a concentration-dependent manner in Leydig cells at 2 h, the duration of submaximal inhibition. This study was undertaken at 3 h of Pb incubation to compare the effects at maximal metal inhibition of steroidogenesis. Quantitatively a 3-h Pb incubation with MA-10 cells resulted in higher decreases in human chorionic gonadotropin (hCG)-stimulated progesterone production, expression of StAR protein, and the activity of 3beta-HSD compared to 2 h. In contrast, lead inhibited dibutyryl cAMP (dbcAMP)-stimulated progesterone production but lacked this effect at 2 h. Surprisingly, Pb at 3 h of incubation did not affect P450scc enzyme activity, yet this enzymatic activity was inhibited at 2 h. Data indicate that incubation time is a factor in Pb-induced alterations in MA- 10 cell steroidogenesis.
Huang
Bu-Miin
BM
Department of Cell Biology and Anatomy, National Cheng Kung University Medical College, Tainan, Taiwan.
Lai
Hung-Yan
HY
Liu
Ming-Yie
MY
D015096:3-Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006888:Hydroxycholesterols / Q000494:pharmacology; D015151:Immunoblotting; D007854:Lead / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D007984:Leydig Cell Tumor; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D011863:Radioimmunoassay; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D007854:Lead; D011374:Progesterone; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases