For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, INTRODUCTION ACTH stimulates cortisol synthesis and secretion by regulating multiple steps in the steroidogenetic pathway including an increase of the number of low-density lipoprotein (LDL) receptors and the cleavage of the side-chain of cholesterol converting it to pregnenolone, the first and rate-limiting step in cortisol production. Type 1 FGD-syndrome is the result of mutations of the MC2R itself. Mutations of this protein result in the type 2 familial glucocorticoid deficiency (FGD) (FGD) syndrome. To activate ACTH the MC2R needs the presence of a small trans-membrane protein, the MC2 accessory protein (MRAP). Circadian rhythm of cortisol secretion is ensured by the central and peripheral local adrenal clock system. ACTH-mediated cortisol synthesis from the zona fasciculata cells depends on a large number of factors of the adrenal microenvironment, such as chromaffin and immune cells, adipocytes, and adrenal innervation. In the adrenal cortex, it induces aldosterone production from the zona glomerulosa cells. The MC5R exhibits a wide distribution although its levels in the central nervous system are low. The MC3R and the MC4R in the central nervous system regulate food intake and energy homeostasis, and knockout animals for these receptors are obese. Thus, the MC1R is the principal melanocortin receptor in the skin where it regulates its pigmentation. The family of melanocortin receptors includes five members each having characteristic size, tissue distribution, and biological significance.

MC2R belongs to a superfamily of type 1 G protein-coupled receptors. ACTH binds to the highly specific, for ACTH, melanocortin (MC) 2 receptors (MC2R) located on the surface of adrenal zona fasciculata cells producing cortisol. ACTH, a post-translational product of the proopiomelanocortin protein (POMC), is a 39-amino acid peptide, its sequence being highly conserved in mammals. The adrenocorticotropin hormone (ACTH) is synthesized by the corticotroph cells of the anterior pituitary gland.

Secretion of adrenal medulla