Function of corticotropin in the diagnosis of adrenocortical function

2018-09-21

Introduction 

Corticotropin (ACTH or adrenocorticotropic hormone) is a linear coupling of 39 amino acid residues and an important member of the hypothalamic-pituitary-adrenal axis. The production and secretion of ACTH is regulated by cortical hormone and corticotropin-releasing hormone (CRH) in hypothalamus. Overproduction of corticosteroids in turn can affect the pituitary and hypothalamus, reducing their activity. ACTH-related receptors are widely distributed in the central system and immune cells. They have the function of stimulating the development and function of the adrenal cortex, mainly acting on the adrenal cortical bundles and stimulating the secretion of glucocorticoids. ACTH is also related to the circadian rhythm in many organisms.

Pharmacologic action

As a diagnostic aid (adrenocortical function), ACTH combines with a specific receptor on the adrenal cell plasma membrane. In patients with normal adrenocortical function, it stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of cholesterol within the mitochondria. ACTH acts to increase the concentration of corticosteroids within adrenal cells. It is thought that one major mechanism by which ACTH stimulates corticosteroid synthesis is the following: ACTH increases phosphorylase activity; this, in turn, converts glycogen to glucose-1-phosphate at an increased rate. Glucose-1-phosphate is rapidly converted to glucose-6- phosphate, which is metabolized primarily by dehydrogenation. In the process of dehydrogenation reduced (triphosphopyridine nucleotide) TPN is generated; reduced TPN then stimulates the processes of corticosteroid synthesis.

Function

Under normal conditions, ACTH is released from the pituitary gland at the base of the brain and is used in the adrenal gland.If the adrenal gland is healthy, a single dose of tetrapeptides increases blood cortisol (hydrocortisone) concentrations within 30 minutes. If the adrenal gland is unhealthy, carbon tetrachloride can be injected to check whether the problem is caused by a diseased or damaged adrenal gland or by a lack of pituitary ACTH. ACTH deficiency is a symptom of secondary adrenal insufficiency (inhibition of ACTH production due to hypophysis or hypothalamic impairment or hypothalamic impairment) or stage Ⅲ adrenal insufficiency (hypothalamic disease, decreased release of corticosteroid release hormone (CRH)). In contrast, primary adrenal insufficiency resulted in increased ACTH levels in the adrenal cortex, such as Cushing's syndrome, Nelson's syndrome, and pituitary adrenocorticotropic tumor.

Pharmacokinetics and metabolism

ACTH intravenous or intramuscular injection has the same pharmacological and clinical effects as cortisone.Normal human ACTH concentration <46pg/ml, and the ACTH precursors were slightly different from the ACTH concentration (5-40pmol/L). However, the measurement of ACTH precursors in patients with ectopic ACTH syndrome showed that these precursors were much higher than the ACTH concentration. Cyclic ACTH is measured by pulsating studies, with high ACTH pulses (12 to 30 times per day) and short half-life of ACTH (usually measured in 14 to 35 minutes). ACTH is involved in the synthesis of corticosteroid hormones after binding to multiple receptors in the body.

References:

1. Erika Harno, Anne White. Adrenocorticotropic Hormone. Endocrinology: Adult and Pediatric (Seventh Edition), 2016,129-146.

2. Haynes, R. C., & Berthet, L. (1957). Studies on the mechanism of action of the adrenocorticotropic hormone. Journal of Biological Chemistry, 225(1), 115-124.

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