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Effect of dihydrotestosterone on turnover of alcohol dehydrogenase in rat hepatocyte culture
Author(s) -
Mezey Esteban,
RennieTankersley Lynda,
Potter James J.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270129
Subject(s) - dihydrotestosterone , enzyme , endocrinology , medicine , alcohol dehydrogenase , enzyme assay , chemistry , catabolism , hepatocyte , dehydrogenase , messenger rna , metabolism , testosterone (patch) , biology , biochemistry , hormone , androgen , in vitro , gene
Dihydrotestosterone decreased alcohol dehydrogenase (ADH) activity and enzyme‐protein in rat hepatocytes in culture. This effect was observed after the hepatocytes had been exposed to dihydrotestosterone for 3 days at concentrations of 0.5 μmol/L or higher. Dihydrotestosterone did not decrease alcohol dehydrogenase messenger RNA (mRNA) but, rather, resulted in small increases in ADH mRNA after 3 days of exposure. To further determine the mechanism for the effects of dihydrotestosterone in decreasing the enzyme, the turnover of ADH was determined after incorporation of [ 3 H]‐leucine into the enzyme protein. Dihydrotestosterone did not alter the initial 2‐hour incorporation of [ 3 H]‐leucine into the enzyme protein. Dihydrotestosterone, however, resulted in an increase in the fractional rate of degradation (K d ) of the enzyme from 0.12 ± 0.013 to 0.23 ± 0.004 per hour ( P < .001) accompanied by a much smaller increase in the fractional rate of synthesis (K s ) from 0.12 ± 0.028 to 0.17 ± 0.031 per hour( P > .05). Hence, the mechanism for the fall in ADH in the presence of dihydrotestosterone is an increase in enzyme degradation which is not accompanied by a sufficient increase in enzyme synthesis.