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. 2016 Jul 20;7:98. doi: 10.3389/fendo.2016.00098

Figure 1.

Figure 1

Direct and indirect effects of ACTH on steroidogenesis in the adrenal gland. ACTH exerts a direct stimulatory effect on adrenocortical cells via melanocortin type 2 receptors (MC2R). Activation of MC2R increases secretion of steroid hormones, vascular endothelial growth factor (VEGF), and epoxyeicosatrienoic acids (EETs). Angiogenesis induced by VEGF, an endothelial cell-specific mitogen factor, allows adrenal tissue growth in response to ACTH. Increase in adrenal blood flow elicited by EETs, which are potent vasorelaxant agents, favors steroid production. In rats, ACTH also activates adrenal mast cells inducing local release of histamine and serotonin (5-HT). These factors modulate the tonicity of adrenal arterioles and, thus, the adrenal blood flow that indirectly influences the steroidogenesis. In addition, 5-HT stimulates steroid secretion through activation of different 5-HT receptor subtypes expressed by normal and tumor human adrenocortical cells.