REGULATION OF ADRENAL CORTICOSTEROID PRODUCTION



REGULATION OF ADRENAL CORTICOSTEROID PRODUCTION







CORTISOL SECRETION


ADRENOCORTICOTROPIC HORMONE

ACTH is a 39-amino-acid peptide that is produced in the anterior pituitary. It is synthesized as part of a larger molecular weight precursor peptide known as proopiomelanocortin (POMC). This precursor peptide is also the source of β-lipotropin (β-LPH). In addition, ACTH and β-LPH are cleaved further to yield α- and β-melanocyte-stimulating hormone (α-MSH and β-MSH, respectively), corticotropin-like intermediate lobe peptide (CLIP), γ-LPH, β- and γ-endorphin, and enkephalin (see Chap. 14). The POMC precursor peptide is found in a variety of extrahypothalamic tissues, including the gastrointestinal tract, numerous tumors, and the testis. It is secreted in small amounts from the anterior pituitary gland and does not bind significantly to the ACTH receptor.

ACTH is the primary regulator of adrenal cortisol secretion. ACTH acts through a specific G protein–coupled receptor to increase levels of cAMP (cyclic or 3′,5′-adenosine monophosphate).26 The cAMP has short-term effects (minutes to hours) on cholesterol transport into mitochondria2 but longer term effects (hours to days) on transcription of genes encoding the enzymes required to synthesize cortisol.27 The transcriptional effects occur, at least in part, through increased activity of protein kinase A, which phosphorylates transcriptional regulatory factors, not all of which have been identified. ACTH also influences the remainder of the steps in steroidogenesis as well as the uptake of cholesterol from the plasma lipoproteins and the maintenance of the size of the adrenal glands. In addition to these effects on the adrenal gland, it also stimulates melanocytes and results in hyperpigmentation when secreted in excess (see Chap. 14).

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Aug 25, 2016 | Posted by in ENDOCRINOLOGY | Comments Off on REGULATION OF ADRENAL CORTICOSTEROID PRODUCTION

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