Adrenocorticotropin

•    Also called Adrenocorticotropic Hormone

(ACTH), corticotropin

•    Concerned with the growth and functioning of adrenal cortex

•    Chemistry:

– Single polypeptide with 39 aminoacids

•    First 23 amino acids from N-terminal contains biological activity

–  Molecular weight 4500

–  Occurs in two forms

•     α-corticotropin

•     β-corticotropin

•     ACTH is synthesized from a glycoprotein called Proopiomelano cortin (POMC) peptide

•     POMC is hydrolyzed by different enzymes to form:

–  ACTH

–  β-Lipotropin

–  β-Endorphins 

–  Melanocyte Stimulating Hormone (MSH) etc.

•    Mechanism of Action

•    Ca²⁺ ion dependant activation of cAMP

– Increased transcription and translation

•    Growth of adrenal cortex

–  Increased phosphorylation and activation of cholesterol estrase

• Free cholesterol is raised in adrenal cortex

–  Increased cAMP activates hormone sensitive lipase

•     Increased lypolysis and free fatty acids

•     Biochemical Functions:

•     Main function of ACTH is the development and secretions of adrenal cortex

–  Increased synthesis of corticosteroids

–  Increased release of corticosteroids from adrenal cortex

•    Stimulate synthesis and secretion of glucocorticoids

–  Promote uptake of cholesterol from plasma lipoproteins into fasciculata cells or adrenal cortex

–  Elevates the levels of free cholesterol

–  Promotes binding of cholesterol to cyctochrome P₄₅₀ and helps in hydroxylation of cholesterol

•    Promotes conversion of cholesterol to pregnenolone in adrenal cortex

•    Activates protein synthesis

•    Activates lipase of adipose tissue

–  Increases lipolysis and amount of free fatty acids

•     Increases ketogenesis

•     Activates dehydrogenases of HMP and increased concentration of NADPH required for hydroxylation

•     Excessive production of ACTH cause Cushing’s syndrome

–  Elevated cortisol levels from adrenal cortex

Hyperpigmentation