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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2628-2633, October 2004


Nutrient Metabolism

Estrogen Controls Branched-Chain Amino Acid Catabolism in Female Rats1

Mariko Obayashi, Yoshiharu Shimomura*, Naoya Nakai{dagger}, Nam Ho Jeoung, Masaru Nagasaki**, Taro Murakami*, Yuzo Sato** and Robert A. Harris2

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202; * Department of Materials Science and Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan; {dagger} Department of Biochemistry, Faculty of Medicine, Mie University, Mie 514-8507, Japan; and ** Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University, Aichi 470-0195, Japan

2To whom correspondence should be addressed. E-mail: raharris{at}iupui.edu.

A diurnal rhythm occurs in the activity state of branched-chain {alpha}-keto acid dehydrogenase complex (BCKDC) in female but not male rats. We attempted to determine the role played by ovarian hormones in this difference in enzyme regulation. A series of experiments examined the effects of the 4-d estrous cycle, ovariectomy, and replacement of female sex steroids on the catabolism of BCAAs. A proestrous decrease in the activity state of the complex corresponded to an increase in the plasma 17ß-estradiol level. Withdrawal of gonadal steroids by ovariectomy resulted in an increase in the activity state of BCKDC and a decrease in the activity of the branched-chain {alpha}-keto acid dehydrogenase kinase (BDK). However, 17ß-estradiol reversed these effects, resulting in an increase in the BDK activity, thereby decreasing the activity of the complex. Progesterone administration was ineffective. The changes in the percentage of active BCKDC caused by 17ß-estradiol withdrawal and replacement resulted from changes in the amount of BDK protein associated with the complex and therefore its activity. Thus, the marked diurnal variation in the activity state of BCKDC exhibited by female rats involves estrogenic control of BDK activity. We hypothesize that the 17ß-estradiol–controlled feeding pattern produces these variations in BCKDC activity. This may function in female rats to conserve essential amino acids for protein synthesis.


KEY WORDS: • branched-chain {alpha}-keto acid dehydrogenase complex • kinase • 17ß-estradiol • liver




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