The adrenal cortex produces two primary types of adrenal steroid hormones: the glucocorticoids and mineralocorticoids. Small amounts of other steroids, such as the sex hormones (androgens, estrogens, and progestins), are also produced by the adrenal cortex (see Chapter 30). The adrenocorticosteroids have several important physiological and pharmacological functions. The glucocorticoids (cortisol, corticosterone) are primarily involved in the control of glucose metabolism and the body’s ability to deal with stress. Glucocorticoids have other attributes, such as their ability to decrease inflammation and suppress the immune system. Mineralocorticoids, such as aldosterone, are involved in maintaining fluid and electrolyte balance in the body.
Prescribers can administer adrenal steroids and their synthetic analogs to mimic the effects of their deficient endogenous counterparts. The quantity administered during this hormonal replacement therapy is roughly equivalent to the normal endogenous production and is often referred to as a physiological dose. The use of adrenal steroids in higher doses can capitalize on a particular beneficial effect, such as using glucocorticoids as anti-inflammatory agents. This larger dose is typically referred to as a pharmacological dose in order to differentiate them from the amount used to maintain normal endocrine function.
This chapter discusses the biosynthesis of the adrenal steroids in an effort to show some of the structural and functional similarities between various steroid groups. The basic physiological and pharmacological properties of the glucocorticoids are then addressed, followed by a description of mineralocorticoid function.
Adrenal steroids are manufactured by enzymes located in specific intracellular organelles, such as the mitochondria and smooth endoplasmic reticulum. As shown in Figure 29-1, there are three primary pathways involved in steroid biosynthesis, each leading to one of the major types of steroid hormone.1,2 The mineralocorticoid pathway synthesizes aldosterone, the glucocorticoid pathway synthesizes cortisol, and the androgen/estrogen pathway leads to the synthesis of sex hormones. Although all three pathways are present in the adrenal cortex, the mineralocorticoid and glucocorticoid pathways predominate. The appropriate enzymes for sex hormone biosynthesis are also present in the gonads, where hormones are synthesized in the testes (men) or ovaries (women).
Pathways of adrenal steroid biosynthesis. Cholesterol is the precursor for the three steroid hormone pathways. Note the similarity between the structures of the primary mineralocorticoid (aldosterone), the primary glucocorticoid (cortisol), and the sex hormones (testosterone, estradiol).
Steroid hormones bear a remarkable structural similarity to one another (see Fig. 29-1). The precursor for steroid biosynthesis is cholesterol. Consequently, all of the steroid hormones share the same basic chemical configuration as their parent compound. This fact has several important physiological and pharmacological implications. First, even relatively minor changes in the side chains of the parent compound create steroids with dramatically different physiological effects. For instance, the addition of only one hydrogen atom in the sex ...