Question 1

What is the Meaning of 11β-HSD2?

Accepted Answer

11β-HSD2, or 11-beta-hydroxysteroid dehydrogenase type 2, is a pivotal enzyme responsible for inactivating the potent glucocorticoid cortisol into its metabolically inert form, cortisone. This enzymatic action is essential for protecting mineralocorticoid receptors from the activating effects of cortisol, ensuring that aldosterone primarily regulates these receptors in target tissues.

Question 2

What is the Context of 11β-HSD2?

Accepted Answer

This enzyme is predominantly expressed in mineralocorticoid target tissues, including the renal collecting ducts, colon, salivary glands, and the placenta. Its localized presence within these organs is critical for safeguarding their delicate electrolyte and fluid regulatory mechanisms from the potent, non-selective effects of circulating cortisol, thereby maintaining physiological homeostasis.

Question 3

What is the Significance of 11β-HSD2?

Accepted Answer

The proper function of 11β-HSD2 holds considerable clinical importance, as its deficiency or inhibition can lead to conditions resembling primary hyperaldosteronism, such as apparent mineralocorticoid excess (AME) syndrome. This enzymatic activity is fundamental for maintaining normal blood pressure and preventing electrolyte imbalances, directly influencing patient well-being and diagnostic pathways in hypertension.

Question 4

What is the Mechanism of 11β-HSD2?

Accepted Answer

11β-HSD2 catalyzes the conversion of active cortisol to inactive cortisone by oxidizing the 11β-hydroxyl group of cortisol, a process that requires NAD+ as a cofactor. This metabolic transformation ensures that mineralocorticoid receptors, which possess a high affinity for both aldosterone and cortisol, are primarily activated by aldosterone, thereby preserving its specific physiological actions on sodium reabsorption and potassium excretion.

Question 5

What is the Application of 11β-HSD2?

Accepted Answer

Clinically, understanding 11β-HSD2 activity is instrumental in differentiating causes of hypertension, particularly those related to mineralocorticoid excess. Substances like glycyrrhizic acid, found in licorice, can inhibit this enzyme, mimicking the effects of hyperaldosteronism and serving as a diagnostic clue in specific patient presentations. The enzyme also plays a vital protective role in fetal development by inactivating maternal cortisol, preventing its detrimental effects on the developing fetus.

Question 6

What is the Metric of 11β-HSD2?

Accepted Answer

The functional integrity of 11β-HSD2 is often assessed by measuring the urinary ratio of cortisol to cortisone, known as the F/E ratio, which provides an indirect but informative biomarker of its activity. Genetic analysis of the HSD11B2 gene can confirm congenital defects in patients presenting with suspected apparent mineralocorticoid excess. Concurrent assessment of plasma renin activity and aldosterone levels further refines the diagnostic picture in individuals with hypertension and electrolyte disturbances.

Question 7

What is the Risk of 11β-HSD2?

Accepted Answer

Dysregulation of 11β-HSD2 carries significant clinical risks, most notably the development of apparent mineralocorticoid excess (AME) syndrome, characterized by severe hypertension, hypokalemia, and metabolic alkalosis due to uncontrolled cortisol action on mineralocorticoid receptors. Exogenous inhibitors, such as chronic high intake of licorice, can induce a similar syndrome, necessitating careful dietary and medication counseling to prevent adverse cardiovascular and electrolyte disturbances when managing patients.

11β-HSD2

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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