Tributyltin disturbs bovine adrenal steroidogenesis by two modes of action.
Tributyltin, an environmental pollutant, affected adrenal steroid hormone biosynthesis by two modes of action. Treatment of bovine adrenal cultured cells with 10-100 nM tributyltin for 48 h suppressed cortisol and androstenedione secretion, but induced the accumulation of 17alpha-hydroxyprogesterone and deoxycortisol, indicating that the P450(C21) and P450(11beta) activities were specifically suppressed. Direct inhibition of the enzymatic activities due to tributyltin was not observed in isolated organelles of untreated cells at concentrations less than 10 microM. Western blotting experiments using specific antibodies against steroidogenic enzymes showed that treatment with 1-100 nM tributyltin caused a decrease in cellular P450(C21) and P450(11beta) protein levels, and real-time PCR experiments showed that the decrease in protein content was attributable to decreases in mRNA of the enzymes. Tributyltin at concentrations higher than 100 nM suppressed all steroid biosynthesis in the adrenal cells. This suppression was closely correlated to the decrease in steroidogenic acute regulatory protein. Since nanomolar concentrations of tributyltin disturbed steroidogenesis in mammalian cells, there is the possibility that steroid hormone synthesis in polluted wild animals is affected by this compound.
Yamazaki
Takeshi
T
Faculty of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama 739-8524, Japan. takey@hiroshima-u.ac.jp
Shimodaira
Mika
M
Kuwahara
Hifumi
H
Wakatsuki
Hitoshi
H
Horiuchi
Hiroyuki
H
Matsuda
Haruo
H
Kominami
Shiro
S
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000187:drug effects* / Q000201:enzymology; D000098682:Steroidogenic Acute Regulatory Protein
D000305:Adrenal Cortex Hormones; D010750:Phosphoproteins; D012333:RNA, Messenger; D014220:Trialkyltin Compounds; D000098682:Steroidogenic Acute Regulatory Protein; C011559:tributyltin; D002786:Cholesterol Side-Chain Cleavage Enzyme