Cortisol

Cortisol is produced mainly in the zona fasciculata and in small quanities in the zona reticularis of the adrenal cortex, the end product of a cascade of hormones that make up the hypothalamic–pituitary–adrenocortical axis (Fig 47.2). Corticotrophin releasing hormone (CRH) is secreted by the hypothalamus under the influence of cerebral factors. Adrenocorticotrophic hormone (corticotrophin, or simply ACTH) is secreted by the anterior pituitary under the control of CRH to maintain the fascicular and reticular zones of the adrenal cortex and to stimulate the secretion of cortisol. Hypothalamic secretion of CRH and pituitary secretion of ACTH are modulated by cortisol in negative feedback loops.

Adrenal cortex cells have many low-density lipoprotein receptors on their surface. This enables them to take up cholesterol rapidly, from which the adrenal steroid hormones are synthesized (Fig 47.3).

The conversion of cholesterol to pregnenolone is the rate-limiting step in the biosynthesis of cortisol; this conversion is stimulated by ACTH. Cortisol biosynthesis from pregnenolone involves the action of a specific reductase/isomerase and three separate hydroxylase enzymes. Inherited defects of all of these enzymes have been characterized.

Cortisol is an important hormone with effects on many tissues in the body. It plays a major role in metabolism by promoting protein breakdown in muscle and connective tissue and the release of glycerol and free fatty acids from adipose tissue. Thus, cortisol provides the substrates necessary for gluconeogenesis, which it promotes in the liver.

Natural or synthetic steroids with cortisol-like effects are called glucocorticoids. Such compounds can act as anti-inflammatory or immunosuppressive agents. Synthetic glucocorticoids have found therapeutic applications in a wide range of clinical situations, e.g. asthma and connective tissue disorders.

Adrenal androgens