Glucocorticoid synthesis is under inhibitory feedback control by the hypothalamus and the pituitary. Hypothalamic release of corticotropin-releasing hormone (CRH) occurs in response to endogenous or exogenous stress. CRH stimulates the cleavage of the 241–amino acid polypeptide proopiomelanocortin (POMC) by pituitary-specific prohormone convertase 1 (PC1), yielding the 39–amino acid peptide ACTH. ACTH is released by the corticotrope cells of the anterior pituitary. The release of CRH, and subsequently ACTH, occurs in a pulsatile fashion that follows a circadian rhythm under the control of suprachiasmatic nucleus (SCN), with additionalregulation by a complex network of cell-specific clock genes. Reflecting the pattern of ACTH secretion, adrenal cortisol secretionexhibits a distinct circadian rhythm, starting to rise in the early morning hours prior to awakening, with peak levels in the morning and low levels in the evening .
Reference: Harrison -21 st edition
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