Adrenocortical Hormone Regulation

  • As discussed in Adrenocortical Hormone Biosynthesis, synthesis of all corticosteroids require the presence of Cholesterol Desmolase whose expression is ACTH-dependent. Furthermore, ACTH is a critical trophic factor for the adrenal cortex without which the organ undergoes progressive atrophy. Consequently, all corticosteroid biosynthesis requires ACTH and is thus to a certain extent under ACTH-dependent regulation. However, the degree of ACTH-dependence varies for different corticosteroids allowing for unique, hormone-specific regulatory mechanisms to exist.
Hormone-specific Regulation
  • Mineralocorticoids
    • Biosynthesis of mineralocorticoids, such as aldosterone, requires only very low levels of ACTH, indicating that cholesterol desmolase is not the rate-limiting enzyme of the biosynthetic pathway. Consequently, aldosterone synthesis is not physiologically regulated by modulation of ACTH levels and is only affected in the context of total ACTH absence, a pathological scenario. Instead, aldosterone synthesis is physiologically regulated by the renin-angiotensin-aldosterone system and serum potassium levels.
  • glucocorticoids
    • Biosynthesis of glucocorticoids, such as cortisol, appears to be primarily regulated by ACTH levels, indicating that Cholesterol Desmolase is the rate-limiting enzyme of the biosynthetic pathway. Therefore, physiological glucocorticoid synthesis and release largely matches that of ACTH.
  • Adrenal Androgens
    • Like all other corticosteroids adrenal androgens require at least some ACTH for their synthesis; however, their variations do not appear to match that of ACTH levels. Consequently, although hormone-specific regulatory mechanism appear to exist, they are currently poorly understood.