The hypothalamic-pituitary-adrenal axis The hypothalamic-pituitary-adrenal axis. The main sites for feedback control by plasma cortisol are the pituitary gland (1) and the hypothalamic corticotropin-releasing center (2). Feedback control by plasma cortisol also occurs at the locus coeruleus/sympathetic system (3) and may involve higher nerve centers (4) as well. There may also be a short feedback loop involving inhibition of CRH by ACTH (5). Hypothalamic neurotransmitters influence CRH release; serotoninergic and cholinergic systems stimulate the secretion of CRH and ACTH; α-adrenergic agonists and γ-aminobutyric acid (GABA) probably inhibit CRH release. The opioid peptides β-endorphin and enkephalin inhibit, and vasopressin and angiotensin II augment, the secretion of CRH and ACTH. β-LPT, β-lipotropin; LC, locus coeruleus; NE, norepinephrine; POMC, proopiomelanocortin; SNS, sympathetic nervous system. (Reproduced with permission from W Arlt: Disorders of the adrenal cortex. In: Jameson JL, ed. Harrison’s Endocrinology. New York, NY: McGraw-Hill; 2013.) Source: Adrenal Disorders, Pediatric Practice: Endocrinology, 2e Citation: Kappy MS, Allen DB, Geffner ME. Pediatric Practice: Endocrinology, 2e; 2013 Available at: http://accesspediatrics.mhmedical.com/DownloadImage.aspx?image=/data/books/1082/kap_ch5_f004.png&sec=61462852&BookID=1082&ChapterSecID=61462816&imagename= Accessed: October 21, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved