Question

A patient appears to have “white coat” hypertension- very high blood pressure when they come to the doctor’s office. When they are relaxed at home, blood pressure is fairly normal. Blood tests show that the patient has high sodium levels and low potassium levels during these periods of hypertension. Additionally, the patient’s medical records also showed that blood pressure rises unusually during fasting and illness as well, and that they had to stop taking an anti-inflammatory drug due to hypertension as a side effect. The physician talks to a colleague who is an endocrinologist specializing in genetics (to the rescue!).

The endocrinologist concluded that the patient might have inherited a mutation that affects the activity of a steroid hormone receptor (Receptor A) that binds to a steroid hormone (Hormone A) that plays an important role in blood pressure regulation. She found that the patient has a mutation that allows Receptor A to be activated even better by a second, related steroid Hormone B. Hormone B can now, by accident, strongly activate Receptor A even within the normal range of blood levels regulated by its negative feedback loop.

• Hormone A: What is Hormone A? What regulates its secretion? What cells secrete it? What is its normal physiological role?
• Hormone B: What is Hormone B? What regulates its secretion? What cells secrete it? What is its normal physiological role?

Answer 1

Hormone A is Aldosterone .

(Aldosterone Receptor is a receptor with equal affinity for mineralocorticoids -(Aldosterone) and glucocorticoids.In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports resulting in the reabsorption of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure,)

Aldosterone Secreation is regulated by renin-Angiotensin system.

(Renin is secreated by kidney in response to low bp or low sodium levels,Renin activates the renin–angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into angiotensin II by Angiotensin converting enzyme.angiotensin 2 stimulates aldosterone secreation)

Aldosterone is secreated by Zona Glomerulosa of Adrenal glands

Normal physiological role :Aldosterone serves as the principal regulator of the salt and water balance of the body. It also has a small effect on the metabolism of fats, carbohydrates, and proteins.It causes sodium and water retention, which causes increased blood volume, and a subsequent increase in blood pressure .

Hormone B is Cortisol.

Aldosterone receptors have equall affinity for both Aldosterone and Cortisol ,But the mineralocorticoid(Aldosterone) receptor is protected from cortisol by co-localization of an enzyme, corticosteroid 11-beta-dehydrogenase isozyme 2 (11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone.

Inactivating mutations of the 11β-HSD2 gene and pharmacological inhibition of the enzyme allow cortisol to activate Aldosterone receptor

Cortisol secreation is regulated by the hypothalamic hormone, Corticosteroid Releasing Hormone(CRH), and the pituitary hormone, Adreno Cortico Tropic Hormone(ACTH), in the hypothalamus-pituitary-adrenal axis

It is secreated by zona fasciculata of adrenal gland.

Normal Physiological role:Cortisol can help control blood sugar levels, regulate metabolism, help reduce inflammation, and assist with memory formulation. It has a controlling effect on salt and water balance and helps control blood pressure.