20beta-hydroxysteroid dehydrogenase catalyzes ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of adult male rats.
We examined the catalytic properties and physiological function of an enzyme responsible for the ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of adult male rats. Progesterone, 17alpha-hydroxyprogesterone, cortisone and cortisol, which have a ketone group at 20-position of C21-steroids, were potent inhibitors for ketone-reduction of acetohexamide in liver microsomes of adult male rats. Progesterone was also found to inhibit competitively the ketone-reduction of acetohexamide, suggesting that the ketone-reduction of acetohexamide and progesterone is catalyzed by the same enzyme. When progesterone was used as a substrate, 20beta-hydroxysteroid dehydrogenase present in liver microsomes of adult rats, such as acetohexamide reductase, exhibited a male-specific and androgen-dependent activity. Furthermore, a significant correlation was observed between the activities of 20beta-hydroxysteroid dehydrogenase and acetohexamide reductase in liver microsomes of individual male rats at various ages. Based on all results, we conclude that 20beta-hydroxysteroid dehydrogenase catalyzes the ketone-reduction of acetohexamide in liver microsomes of adult male rats.
Takada
H
H
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Kumamoto 862-0973, Japan.
Otagiri
M
M
Imamura
Y
Y
D000092:Acetohexamide / Q000493:pharmacokinetics*; D000375:Aging / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D003349:Cortisone Reductase / Q000378:metabolism*; D005260:Female; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007659:Ketones / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D007004:Hypoglycemic Agents; D007659:Ketones; D000429:Alcohol Oxidoreductases; C064152:acetohexamide reductase; D003349:Cortisone Reductase; D000092:Acetohexamide