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Biosynthesis of Endogenous Cardiac Glycosides by Mammalian Adrenocortical Cells: Three Steps Forward

¹ Department of Physiology, School of Medicine, University of Maryland, Baltimore, Baltimore, MD 21201

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2003 was the 50th anniversary of the isolation and identification of the mineralocorticoid aldosterone—a momentous event if only because aldosterone has been widely regarded as the last major metabolically active steroid to be described in the mammalian adrenal gland (1). In this issue of the journal, Qazzaz et al. (2) describe studies that support the possibility of de novo biosynthesis, in the adrenal, of a material whose overall physicochemical, immunocrossreactive, and chromatographic characteristics are indistinguishable from those of the cardiac glycoside (CG) digoxin and its dihydro analog (in which the lactone ring is fully saturated). Using a mouse tumor cell line derived from adrenocortical cells, the authors show that the ¹⁴C label from acetic acid, as well as that from labeled cholesterol, becomes incorporated into the two digoxin-like materials. Moreover, inhibition of hydroxymethylglutaryl (HMG)-CoA reductase with Mevastatin reduced the ¹⁴C labeling of both products while leaving the issue of side chain cleavage unanswered. Although sophisticated analytical methods were not used in the study, the fingerprinting of the endogenous products and the behavior of the ¹⁴C labeling are entirely consistent with the presence of digoxin and dihydrodigoxin or their respective isomers and, therefore, with . . . [Full Text of this Article]

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