Abstract
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, 17α-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, 20β-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 20β-hydroxysteroid dehydrogenase and acetohexamide reductase in liver microsomes of individual male rats at various ages. Based on all results, we conclude that 20β-hydroxysteroid dehydrogenase catalyzes the ketone-reduction of acetohexamide in liver microsomes of adult male rats.
Footnotes
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Send reprint requests to: Dr. Yorishige Imamura, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Kumamoto 862-0973, Japan.
- Abbreviations:
- 20α- and 20β-HSD
- 20α- and 20β- hydroxysteroid dehydrogenase
- CYP
- cytochrome P450
- ANOVA
- analysis of variance
- HPLC
- high-performance liquid chromatography
- Received March 26, 1998.
- Accepted June 3, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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