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In female rats, ovariectomy (OVX) is associated with increased body fat and insulin resistance, and estradiol replacement prevents these alterations. These metabolic changes related to the estrogen-deficient state might be due, in part, to alterations in skeletal muscle substrate metabolism. We tested the hypothesis that estradiol affects the regulation of enzymes involved in substrate oxidation and storage within skeletal muscle. Specifically, we examined enzymes involved in the regulation of glycogen synthesis (glycogen synthase [GS]), glycolysis (phosphofructokinase [PFK]), tricarboxylic acid cycle activity (citrate synthase [CS]), and [beta ]-oxidation ([beta ]-hydroxyacyl-CoA dehydrogenase [[beta ]-HADH]). Twenty-two, female Sprague-Dawley rats (7 to 8 weeks old) were separated into 3 groups: OVX + placebo (P; n = 8), OVX + estradiol (E2; n = 8), and sham-operated (S; n = 6). Rats from E2 and P groups were pair-fed to the S group to control for OVX-induced changes in food intake. After 16 days, activities of GS, PFK, CS, and [beta ]-HADH were measured in vastus medialis muscle. GS fractional velocity was significantly lower (P [lt ] .05) in P (mean [plusmn] SE; 39.7% [plusmn] 6.2%) compared with both S (61.9% [plusmn] 8.8%) and E2 (65.8% [plusmn] 8.4%) rats. In addition, E2 rats (41.4 [plusmn] 2.0) had significantly higher (P [lt ] .05) CS activity than P (34.9 [plusmn] 2.0) and S (33.9 [plusmn] 1.4 [mu ]mol/min/g) groups. There was no effect of OVX or estradiol replacement on [beta ]-HADH or PFK. Our results suggest that, independent of alterations in food intake, estradiol availability affects the regulation of enzymes involved in nonoxidative glucose disposal (GS) and oxidative metabolism (CS) in skeletal muscle.
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☆Supported in part by a grant from the Hughes Endeavor for Life Science Excellence (HELiX; to T.B.) and an American Heart Association Postdoctoral Fellowship (to A.T.).
© 2002 Published by Elsevier Inc. All rights reserved.