Pharmacology of Cortisone, Cortisol (hydrocortisone) and Their New Analogues

In man the essential functions of the adrenal cortex stem from at least two hormones, cortisol (hydrocortisone) and aldosterone, these differing in their quality of action, mode of secretory regulation, and probable site of production within the gland. The adrenal sex hormones are of relatively minor physiological importance and will not be considered here. The new synthetic analogues of cortisol are best assessed in relation to the essential duality of function of the adrenal cortex as revealed by the actions of its two principal hormones. The first function is concerned with a number of homoeostatic processes and with resistance to stress and is served by the secretion of cortisol. In the body cortisol is reversibly interconvertible with cortisone and is probably the active form of the hormone. Cortisol and cortisone, with their almost identical actions, are called glucocorticoids for their effects on carbohydrate metabolism. Though Ingle (1950) has likened use of the word glucocorticoid for these steroids to describing an elephant by the shape of its tail, yet it remains a useful generic term to cover all those diverse actions of cortisol and its analogues which seem to be inseparably linked with their carbohydrate effects. The second or mineralocorticoid function of the adrenal cortex is concerned with the regulation of sodium and potassium balance, and depends largely on the secretion of aldosterone. A similar but less potent mineralocorticoid is desoxycorticosterone (DOC) which, though easily synthesized and used therapeutically as the acetate (DOCA), is secreted only in small amounts by the adrenal cortex. Further to their glucocorticoid properties, cortisol and cortisone also have a weak mineralocorticoid activity, which assumes an increasing importance when they are being produced in excess as in Cushing's syndrome, or administered in large doses Intermediate in quality of action between cortisolVand aldosterone, but much less potent, is corticosterone (Compound.B). Though it is the predominant glucocorticoid in a number of mammalian species, in man it is of little importance for only small amounts are secreted (about i mg. a day) (Migeon et al., 1956).