Chapter 46: Adrenocorticotropic Hormone, Adrenal Steroids, and the Adrenal Cortex

INTRODUCTION

The major physiological and pharmacological effects of ACTH result from the increase in circulating levels of adrenocortical steroids that ACTH causes. Synthetic derivatives of ACTH are used principally in the diagnostic assessment of adrenocortical function. Because corticosteroids mimic the therapeutic effects of ACTH, synthetic steroids generally are used therapeutically instead of ACTH.

Corticosteroids and their biologically active synthetic derivatives differ in their metabolic (glucocorticoid) and electrolyte-regulating (mineralocorticoid) activities. These agents are used at physiological doses as replacement therapy when endogenous production is impaired. Glucocorticoids potently suppress inflammation, and their use in inflammatory and autoimmune diseases makes them among the most frequently prescribed classes of drugs. Because glucocorticoids exert effects on almost every organ system, their administration and withdrawal may be complicated by serious side effects. Therefore, the decision to institute therapy with systemic glucocorticoids always requires careful consideration of the relative risks and benefits in each patient.

ABBREVIATIONS

CORTICOTROPIN

Human ACTH, a peptide of 39 amino acids, is synthesized as part of a larger precursor protein, POMC, and is derived from the precursor by proteolytic cleavage at dibasic residues by the serine endoprotease, prohormone convertase 1 (also known as prohormone convertase 3) (Figure 46–1). Other biologically important peptides, including endorphins, lipotropins, and the MSHs, also are produced by proteolytic processing of the same POMC precursor (see Chapter 20 and Takahashi and Mizusawa, 2013).