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Adrenal hormone synthesis inhibitors or AHSIs are a group of medications which basically inhibit the synthesis of adrenocortical hormones, more specifically cortisol, which is a glucocorticoid hormone produced by the adrenal cortex.
Normally, the hypothalamus, which is located at the base of the brain, secretes corticotropin-releasing hormone, known as CRH, which stimulates the pituitary gland to secrete adrenocorticotropic hormone, known as ACTH.
ACTH, then, travels to the pair of adrenal glands, on top of each kidney, where it specifically targets cells in the adrenal cortex.
This causes the adrenocortical cells to take up cholesterol from the blood, and it also stimulates an enzyme called cholesterol desmolase inside these cells, which converts cholesterol to pregnenolone.
Then, another enzyme called 3 beta- hydroxysteroid dehydrogenase, (or 3 beta- HSD) turns some of this pregnenolone into progesterone.
17 alpha hydroxypregnenolone is then turned into 17 alpha hydroxyprogesterone by the enzyme 3 beta- hydroxysteroid dehydrogenase.
Then, all of the 17 alpha hydroxyprogesterone is turned into 11 deoxycortisol by the enzyme 21 hydroxylase.
11 deoxycortisol is finally turned into cortisol by the enzyme 11 beta-hydroxylase.
In times of stress, the body needs to have plenty of energy substrates around, so cortisol increases gluconeogenesis, which is the synthesis of new glucose molecules, proteolysis, which is the breakdown of protein and lipolysis, which is the breakdown of fat.
Adrenal hormone synthesis inhibitors are medicinal drugs that act to suppress the production of adrenal hormones. These drugs can be used to manage conditions where excess adrenal hormone production leads to symptoms such as Cushing's syndrome or Conn's syndrome. There are a variety of adrenal hormone synthesis inhibitors available, with different mechanisms of action and potencies. Some common examples include ketoconazole, metyrapone, and etomidate. Selection of the most appropriate drug depends on the individual patient's condition and other factors such as other medications being taken.
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