Pathways

Corticotropin, also known as ACTH or adrenocorticotropic hormone, is a peptide tropic hormone synthesized by the anterior pituitary gland in response to the release of corticotropin-releasing hormone (CRH) from the hypothalamus. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (MSH), and β-endorphin. As an essential component of the hypothalamic-pituitary-adrenal axis, corticotropin is primarily responsible for increasing the adrenal cortex production of cortisol in response to stress. The ACTH receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates pKA (protein kinase A) which phosphorylates downstream effectors that lead to androgen and cortisol production.

Corticotropin, also known as ACTH or adrenocorticotropic hormone, is a peptide tropic hormone synthesized by the anterior pituitary gland in response to the release of corticotropin-releasing hormone (CRH) from the hypothalamus. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (MSH), and β-endorphin. As an essential component of the hypothalamic-pituitary-adrenal axis, corticotropin is primarily responsible for increasing the adrenal cortex production of cortisol in response to stress. The ACTH receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates pKA (protein kinase A) which phosphorylates downstream effectors that lead to androgen and cortisol production.

Corticotropin, also known as ACTH or adrenocorticotropic hormone, is a peptide tropic hormone synthesized by the anterior pituitary gland in response to the release of corticotropin-releasing hormone (CRH) from the hypothalamus. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (MSH), and β-endorphin. As an essential component of the hypothalamic-pituitary-adrenal axis, corticotropin is primarily responsible for increasing the adrenal cortex production of cortisol in response to stress. The ACTH receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates pKA (protein kinase A) which phosphorylates downstream effectors that lead to androgen and cortisol production.

Cortisone acetate is a steroid hormone approved by the FDA since 1950. It is used for the relief of a wide variety of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and gastrointestinal diseases and disorders. This molecule is a prodrug and is activated by a dehydrogenase in the liver. Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. Cortisone acétate also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counseled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections. Since it is a drug used in many different conditions it is administered as an intramuscular injection and oral capsules.