Adrenal Cortex Cholesterol and Steroid Hormone Production

• Corticosteroids are prescribed to reduce inflammation and have a minor role in increasing vascular tone in the heart.

• Cortisol stress/trauma response: hypothalamus releases CRH (Corticotropin-releasing hormone) which makes anterior pituitary release ACTH (Adrenocorticotropic hormone), adrenal cortex makes cortisol.

• Increased cortisol levels have negative feedback to both hypothalamus and anterior pituitary to stop CRH and ACTH respectively.

• ACTH level peaks before cortisol level due to its role in triggering cortisol release.

• During sleep, ACTH and cortisol levels are low, but they peak right before waking up.

• ACTH regulates cortisol synthesis by binding to the melanocortin 2 receptor (GPCR) and activating adenyl cyclase, increasing cAMP, which then triggers the release of cholesterol esters from lipid droplets and their conversion into cholesterol.

• Cortisol synthesis is inhibited in the kidneys by converting cortisol into cortisone through 11 beta hydroxysteroid dehydrogense (11BOHSD), preventing cortisol from binding to the mineralocorticoid receptor (MR) and activating it, which would result in retaining Na, having high blood pressure, and hypertension.

• Pts who eat a lot of liquorice have high blood pressure because licorice inhibits 11BOHSD, preventing cortisol from getting converted into cortisone, allowing cortisol to bind to MR, and retaining Na.

• Cushing's syndrome is caused by excess glucocorticoids, which can be caused by exogenous therapeutic use or tumors of the pituitary or adrenal glands, resulting in symptoms such as red cheeks, receding hairline, striae, moon face, pendulous abdomen, poor muscle development, poor wound healing, hypoglycemia, osteopenia/osteoporosis, proximal myopathy, and hypoadrenalism.

• Adrenal cortex makes cortisol in response to ACTH, which is released from the anterior pituitary in response to CRH from the hypothalamus.

• Adrenal medulla is the inner part of the adrenal gland and is of neuronal origin, making up 10-20% of the gland.

• Adrenal medulla secretes catecholamines, which are stored in granules and are quickly released when needed, unlike steroid hormones, which are secreted by diffusion and not stored.

• Adrenergic receptors are activated by catecholamines, leading to increased glucose production, glycogenolysis, lipolysis, bronchioles dilation, heart rate and contraction increase, and vasoconstriction.

• Catecholamines are released in response to sympathetic nervous system stimulation, and their biosynthetic pathway includes tyrosine hydroxylation, which is the limiting step.

• Epinephrine and norepinephrine are the main catecholamines, with different effects on adrenergic receptors, including increased glucose production, increased heart rate and contractility, and vasoconstriction.

• Pheochromocytoma is a tumor of the adrenal medulla that produces too much catecholamines, resulting in symptoms such as headaches, chest pain, extreme anxiety, cold perspiration, and hypertension.

• Beta-blockers are antagonists of catecholamines, competing with them for binding to adrenergic receptors and preventing their stimulation, making them useful for treating hypertension.

• Amphetamines are agonists of catecholamines, stimulating the adrenergic receptor and mimicking the effects of epinephrine.

• The adrenal cortex consists of three layers: Zona glomerulosa, Zona fasciculata, and Zona reticularis.

• Zona glomerulosa is responsible for aldosterone synthesis, Zona fasciculata for cortisol synthesis, and Zona reticularis for androgens synthesis.

• Cortisol and aldosterone are steroid hormones with different functions.

• Cortisol is a glucocorticoid that increases plasma glucose levels and has various effects on the body, including on the liver, bone, adipose tissue, skin, and immune system.

• Aldosterone is a mineralocorticoid that regulates salt balance and exerts its effects on the kidney.

• Cortisol and aldosterone have different mechanisms of action: cortisol binds to glucocorticoid receptors, while aldosterone binds to mineralocorticoid receptors.

• Cortisol and aldosterone have similar affinity for mineralocorticoid receptors, but renal tubule cells do not respond to cortisol due to the presence of 11β hydroxysteroid-dehydrogenase, which converts cortisol to cortisone.

• Cortisol and aldosterone synthesis is tightly regulated through different mechanisms, including the CRH-ACTH/hypothalamic-anterior pituitary axis and the renin-angiotensin system.

• Catecholamines, including epinephrine and norepinephrine, are synthesized in the adrenal medulla and are involved in the response to stress.

• Epinephrine and norepinephrine have different effects on the body and act through different receptors.

• Agonists and antagonists of epinephrine and norepinephrine receptors are used in various therapies.

• The adrenal medulla represents 10-20% of the adrenal gland and is of neuronal origin.

• The biosynthetic pathway of catecholamines takes place in the chromaffin cells of the adrenal medulla.

Test your knowledge about the role of cholesterol in the production of steroid hormones in the adrenal cortex. Learn about the transportation of cholesterol, its conversion to pregnenolone, and the production of steroids in mitochondria and cytoplasm.