Cortisol

Cortisol release is stimulated by adrenocorticotrophic hormone (ACTH) released from the anterior pituitary (Fig. 5.4). ACTH secretion is stimulated by hypothalamic corticotrophin-releasing hormone (CRH). Cortisol in turn inhibits ACTH and CRH production (negative feedback).

Activation of the ACTH receptor on the plasma membrane of cells in the zona fasciculata results in the activation of adenylate cyclase and hence increased cyclic AMP levels. This leads to the stimulation of steroidogenic acute regulatory protein (StAR), which mediates the transport of cholesterol through the cytosol to the inner mitochondrial membrane, where it is converted to pregnenolone. This is the rate-limiting step in cortisol synthesis (Fig. 5.3). Activation of adenylate cyclase also results in upregulated gene expression of other enzymes involved in steroid synthesis.

Figure 5.2 Adrenal histology.

Figure 5.3 Biosynthesis of adrenal steroid hormones.

Figure 5.4 Hypothalamic–pituitary–adrenal axis.

Cortisol secretion normally reflects that of ACTH, and is therefore also pulsatile with a circadian rhythm.

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