Mitochondrial regulation of mineralocorticoid biosynthesis by calcium and the StAR protein.

In mammals, all steroids are synthesized from a common precursor, cholesterol. In contrast to polypeptide hormone-secreting cells such as pancreatic or anterior pituitary cells, steroid-producing cells cannot store mature, ready-to-be-delivered hormone in secretory granules because, as a result of their lipophilicity, steroids can diffuse more or less freely across organellar and cellular membranes. To circumvent this difficulty, instead of accumulating end products, steroidogenic cells esterify large amounts of cholesterol after endogenous biosynthesis or internalization of lowor highdensity lipoproteins (LDL or HDL) and package it into intracellular lipid droplets (1). As a corollary to this accumulation of precursor, the cells must be endowed with a system permitting a rapid recruitment of cholesterol, followed by immediate activation of the steroidogenic cascade. This requirement for the ability to generate acute steroidogenic responses appears particularly important in tissues such as the two outer zones of the adrenal cortex, which are involved in reactions to stress (glucocorticoids) and in blood pressure control (mineralocorticoids), although relatively prompt secretory responses to organotropic hormones are also needed in the testis and ovary. The zona glomerulosa of the adrenal cortex produces aldosterone under the control of two main physiological activators, the octapeptide hormone angiotensin II (Ang II) and extracellular potassium (K) (2). In vitro, these agents are able to elicit steroidogenesis within 1–2 min and these kinetics are closely matched by a fast activation of the calcium messenger system within the same time frame in glomerulosa cells (3). In vivo, when Ang II is infused in man, the onset of the increase in plasma aldosterone is observed within 10 min (4). Clearly, the glomerulosa cell is endowed with a system allowing it rapidly to transduce the elicited intracellular messenger changes into cholesterol metabolism. The present article reviews our current knowledge on the mechanisms of cytosolicand mitochondrial-calcium mediated acute aldosterone biosynthesis in glomerulosa cells, in the light of the recent discovery of the steroidogenic acute regulatory (StAR) protein and of its role in other steroidogenic tissues (5). The calcium messenger system in adrenal glomerulosa cells