ADINOCORTICOTROPIC HORMONE.(ACTH)
Adrenocorticotropic hormone (ACTH), also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of corticosteroids and, as its name suggests, cortisol from the adrenal cortex.
It is a polypeptide which is made up of about 39 amino acids.
FUNCTIONS-
ACTH acts through the stimulation of cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex. This results in the synthesis and secretion of gluco- and mineralo-corticosteroids and androgenic steroids. The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor. Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. This ultimately results in stimulation of steroidogenesis.
ACTH acts at several key steps to influence the steroidogenic pathway in the adrenal cortex:
REGULATION-
It is a polypeptide which is made up of about 39 amino acids.
FUNCTIONS-
ACTH acts through the stimulation of cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex. This results in the synthesis and secretion of gluco- and mineralo-corticosteroids and androgenic steroids. The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor. Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. This ultimately results in stimulation of steroidogenesis.
ACTH acts at several key steps to influence the steroidogenic pathway in the adrenal cortex:
- ACTH stimulates lipoprotein uptake into cortical cells. This increases the bio-availability of cholesterol in the cells of the adrenal cortex.
- ACTH increases the transport of cholesterol into the mitochondria and activates its hydrolysis.
- ACTH Stimulates cholesterol side-chain cleavage enzyme, which makes the rate-limiting step in steroidogenesis. This results in the production of pregnenolone.
REGULATION-
- Acts through cAMP secondary messenger system.
- Controlled by CRH/CRF of hypothalamus which is secreted by the paraventricular nucleus. Shows diurnal rhythm.
- Physical and mental stresses also lead to ACTH release.
- Controlled by feedback effect of cortisol. [17]
Normal Results-Normal values: 9 - 52 pg/mL
Note: pg/mL = picograms per milliliter
DISEASE STATES-
Note: pg/mL = picograms per milliliter
DISEASE STATES-
- Addison's disease
- Small cell carcinoma (a common cause of ACTH secreted ectopically)
- Adrenoleukodystrophy
- Congenital adrenal hyperplasia
- Cushing's syndrome
- Nelson's syndrome
- Infantile spasms [18]