Metabolism of glycyrrhetic acid by rat liver microsomes--III. Male-specific glycyrrhetinate dehydrogenase.
Glycyrrhetinate (GA) dehydrogenase localized in microsomes of rat liver catalyses the oxidation and reverse reduction of 18 beta-glycyrrhetic acid (GA), an aglycone of glycyrrhizin and a main component of liquorice, to 3-keto-18 beta-glycyrrhetic acid (3-ketoGA). The enzyme activity was detected in microsomes of adult males, but not in those of adult females. It was not observed in infant males but appeared 6 weeks after birth, increased gradually and reached the maximum level at 12 weeks after birth, whereas it was not detected in the hepatic microsomes of females of any age. The administration of estradiol valerate to intact adult males decreased GA dehydrogenase activity remarkably. Castration of male rats also caused a marked reduction of the activity, but the administration of testosterone proprionate to these rats restored it to close to the normal level. On the other hand, ovariectomy of female rats did not bring the activity into existence, but the injection of testosterone proprionate to the ovariectomized rats brought it into a slight existence, in spite of no appearance of the activity by the treatment of testosterone proprionate to intact adult females. The sex-related difference in the activity in adults was eliminated by hypophysectomy of male and female rats, their microsomal activities after the operation being the same, 20-40% of the activity in intact males. Moreover, the administration of estradiol valerate to the hypophysectomized rats did not affect the activity. These results indicate that GA dehydrogenase is male-specific and regulated by sex-hormones through the pituitary.
Akao
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T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Akao
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T
Aoyama
M
M
Kobashi
K
K
D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002369:Castration; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006034:Glycyrrhetinic Acid / Q000378:metabolism*; D007016:Hypophysectomy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats / Q000254:growth & development; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology
D013739:Testosterone; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C056636:3-alpha-hydroxyglycyrrhetinate dehydrogenase; D006034:Glycyrrhetinic Acid