Aldosterone

Aldosterone provides a comprehensive and detailed review of the problems that have arisen in the course of research on aldosterone, particularly with respect to their physiological roles and clinical implications. Topics covered include the biosynthesis, transport, and metabolism of aldosterone, as well as its biological activity and control of its secretion. A variety of pathological conditions, both acute and chronic, associated with aldosterone is also discussed. This volume is comprised of 10 chapters and opens with a historical background on aldosterone research, with emphasis on the discovery of the function of the adrenal cortex. The next chapter summarizes the methods suitable for the evaluation of aldosterone activity, from investigations of mineral metabolism to determination of the concentration of aldosterone or aldosterone metabolites; estimation of secretion of aldosterone; and examination of aldosterone metabolism. Subsequent chapters explore the biosynthesis, transport, and metabolism of aldosterone; secretion of aldosterone, factors affecting secretion, and how it can be controlled; pathological conditions caused by either an increase or a decrease in aldosterone secretion, including aldosteronism, Conn's syndrome, hypoaldosteronism, and hypomineralocorticism. The therapeutic uses of aldosterone are discussed in the last chapter. This book will appeal to biologists and biochemists.

This book is an open access dissemination of the EU COST Action ADMIRE in Aldosterone/Mineralocorticoid Receptor (MR) physiology and pathophysiology. Aldosterone is the major hormone regulating blood pressure. Alterations in blood levels of aldosterone and genetic mutations in the MR receptor are major causes of hypertension and comorbidities. Many of the drugs in clinical use, and in development for treating hypertension, target aldosterone and MR actions in the kidney and cardiovascular system. The ADMIRE book assembles review chapters from 16 European ADMIRE laboratories providing the latest insights into mechanisms of aldosterone synthesis/secretion, aldosterone/MR physiology and signaling, and the pathophysiological roles of aldosterone/MR activation.

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Most of our knowledge of the physiological control of aldosterone secretion is based on animal experiments and clinical studies which were carried out in the 1950s and early 1960s by a large number of inspired, ingenious and meticulous researchers. Their work has been excellently reviewed by-among others-MULLER (1963), BLAIR WEST et al. (1963), LARAGH and KELLY (1964), GANONG et al. (1966), MULROW (1966), DAVIS (1967) and GROSS (1967). According to the majority of these investigators, aldosterone secretion is primarily regulated by the renin-angiotensin system, with plasma sodium and potassium levels and pituitary secretion of ACTH playing important secondary roles. During the last six years, this hypothesis has been generally accepted and has only occasionally been challenged. The following is an attempt to take-from the perspective of a relatively simple in vitro model-a new look at the efferent axis of the apparently very complex control system maintaining adequate aldosterone production in the mammalian organism. My views are based mainly on a series of experiments which I have performed in order to study more closely the interactions of adrenocortical tissue with substances capable of directly influencing aldosterone bio synthesis.

Sixteen years is a long time, not only in human life but also in the rapid history of contemporary endocrinology. Since the publication of the first edition of this monograph, numerous new lines of research and discoveries have greatly contrib uted to our knowledge of the physiological and pathological regulation of aldos terone biosynthesis in man and animals. The first reports about a sensitive ra dioimmunoassay for plasma aldosterone and about a preparation of dispersed zona glomerulosa cells were published in 1970 (Mayes et al. 1970; Haning et al. 1970). These two developments alone turned out to have a tremendous impact on research in aldosterone physiology (for reviews see Coghlan et al. 1979b; J.F. Tait et al. 1980b). In 1971, atrial natriuretic peptides, somatostatin, and the precursor molecule of ACTH had not yet been discovered. Angiotensin antagonists and con verting-enzyme inhibitors were not yet available. The clinical syndrome of hypo reninemic hypo aldosteronism was unknown. The possible roles of prostaglandins and dopamine in the control of aldosterone pwduction had not been considered. Cyclic AMP was then the only substance with a clearly established second-mes senger function.