stimulates the adrenal cortex to secrete cortisol

Usually, this is a result of treatment with exogenous glucocorticoids at supra-physiologic doses. However, when cortisol levels are high, and 11β-HSD is saturated, cortisol can activate mineralocorticoid receptors. 11β-hydroxysteroid (type II) dehydrogenase by converting cortisol to its inert form cortisone, prevents the cortisol- activation of mineralocorticoid receptors. Cortisol has the potential to bind and activate both the glucocorticoid receptors and aldosterone receptors. Cortisol is released in the blood bound to cortisol binding protein (CBP), which is a globulin protein.

Cortisone (the inactive form of cortisol) is converted by type 1 hydroxysteroid dehydrogenase in the liver to its active form cortisol. The end product of this pathway is Cortisone. Glucocorticoid production in zona fasciculata involves cholesterol desmolase, 17a-hydroxylase, 21-hydroxylase, 11β-hydroxylase. Desmolase, a CYP450 enzyme, exerts its action by catalyzing a break in the cholesterol side chain. The first step in the steroidogenesis pathway occurs in mitochondria StAR (induced by ACTH) moves cholesterol to the inner mitochondrial membrane. The above actions of ACTH increased the available cholesterol pool for steroidogenesis. PKA modifies the activity of specific transcription factors via phosphorylation.ĪCTH actions include, the activation of HMG CoA reductase (the rate-limiting enzyme in cholesterol synthesis), increased LDL-C esters uptake (that are either stored or converted into cholesterol), activation of hormone-sensitive lipase (HSL) and lastly inhibition of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT). This binding results in the activation of adenylyl cyclase, cAMP production, and activation of protein kinase A (PKA). ACTH acts by binding to a G protein-coupled receptor (the melanocortin two receptor- MC2R). Corticotrophin-releasing hormone (CRH) is released from the hypothalamus and stimulates the adrenocorticotropic hormone (ACTH). The release of cortisol is under the feed-back control of the hypothalamic-pituitary-adrenal (HPA) axis.

Stimulates the adrenal cortex to secrete cortisol