Transcript for Adrenal hormone synthesis inhibitors
Adrenal hormone synthesis inhibitors
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.
Now, the synthesis of cortisol starts when pregnenolone and progesterone move into the zona fasciculata.
The enzyme 17 alpha-hydroxylase turns pregnenolone into 17 alpha- hydroxypregnenolone and turns progesterone into 17 alpha hydroxyprogesterone.
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.
Cortisol is also known as the stress hormone.
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.
Cortisol also helps to maintain the blood pressure by increasing the sensitivity of peripheral blood vessels to catecholamines- epinephrine and norepinephrine, and this narrows the blood vessel lumen.
Cortisol helps to dampen the inflammatory and immune response by reducing the production and release of inflammatory mediators, like prostaglandins and interleukins, as well as inhibiting the proliferation of T-lymphocytes.
Finally, cortisol receptors are present in the brain, where their full effect is still actually unclear but might influence things like mood and memory.
Now, in Cushing syndrome, there’s increased cortisol levels over a long period of time.
This could be due to Cushing disease, which is caused by a benign pituitary adenoma that secretes too much ACTH.
Another cause is adrenocortical carcinomas, which overproduce cortisol.
Excess cortisol leads to severe muscle and skin breakdown which are the major protein stores in the body.
Bones are also broken down which could lead to osteoporosis.
It also elevates blood glucose levels, and that leads to high insulin levels.
Insulin, among its many actions, preferentially targets adipocytes or fat cells in the center of the body - around the waist and buttocks. In those cells, the insulin activates lipoprotein lipase, which is an enzyme that helps those adipocytes accumulate more fat molecules. The result is central obesity, which is fat build up in the abdomen, buffalo hump, which is fat build up between the shoulders, and moon facies which is fat build up in the face.
Excess cortisol also dampens the inflammatory and immune response, making individuals more susceptible to infections.