Influence of adrenalectomy and steroid replacement on heart citrate synthase levels.
Aldosterone-dependent changes in citrate synthase (CS) activity have been used as an index of mineralocorticoid target sites. However, adrenalectomy (ADX) resulted in a fall in activity of CS and several other enzymes in rabbit heart, a tissue with glucocorticoid-but not mineralocorticoid-specific receptors. The enzymes included CS (2.03-1.36 U/mg protein, normal----ADX, P less than 0.001), isocitrate dehydrogenase-NADP+ (1.10-0.80 U/mg, P less than 0.002), isocitrate dehydrogenase-NAD+ (0.034-0.020 U/mg, P less than 0.01), and hydroxymethylglutaryl-CoA lyase (0.072 to 0.035 U/mg, P less than 0.001); in contrast, mitochondrial malate dehydrogenase levels were not significantly reduced by adrenal loss. There was also a decrease after surgery in sarcolemmal Na-K-(17.30-12.31 mumol Pi . mg protein-1 . h-1, P less than 0.002) and Mg-ATPase activities (14.16-12.11 mumol Pi . mg protein-1 . h-1, P less than 0.05). However, ADX did not result in a significant change in heart weight per kilogram body weight or recovery of mitochondrial protein per gram heart. CS was also assayed in hearts from ADX animals following acute (90 min) and chronic (3 day) steroid replacement. Although neither acute intravenous aldosterone (10 micrograms/kg) nor dexamethasone (100 micrograms/kg) increased activity, exposure to multiple subcutaneous injections of either steroid over a 3-day period significantly elevated CS above ADX values. The coordinate changes in the levels of several myocardial enzymes associated with energy metabolism is discussed in terms of an adaptation to chronic alterations in energy demands as opposed to specific mineralocorticoid or glucocorticoid receptor-mediated processes.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D002462:Cell Membrane / Q000201:enzymology; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000378:metabolism
D000450:Aldosterone; D003907:Dexamethasone; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D002950:Citrate (si)-Synthase; D013869:Thiolester Hydrolases; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase; D000254:Sodium-Potassium-Exchanging ATPase