Hypertension and the cortisol-cortisone shuttle.

Area of Science:

• Endocrinology
• Molecular Biology
• Physiology

Background:

• 11 beta-Hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is essential for mineralocorticoid receptor specificity by converting cortisol to cortisone.
• Deficiency in 11 beta-HSD2 activity is implicated in apparent mineralocorticoid excess syndrome, characterized by hypertension and hypokalemia.
• Inhibitors of 11 beta-HSD2, like licorice and carbenoxolone, mimic apparent mineralocorticoid excess.

Purpose of the Study:

• To explore the physiological and pathophysiological roles of 11 beta-HSD2.
• To understand the link between 11 beta-HSD2 activity and various hypertensive states.
• To investigate the genetic and epigenetic factors influencing 11 beta-HSD2 function.

Main Methods:

• Review of existing literature on 11 beta-HSD2.
• Analysis of genetic mutations in the HSD11B2 gene.
• Examination of enzyme kinetics and substrate saturation.
• Epidemiological correlation with birth weight and adult hypertension.

Main Results:

• Mutations in HSD11B2 cause inherited apparent mineralocorticoid excess.
• Reduced 11 beta-HSD2 activity is associated with sodium retention in preeclampsia, renal disease, and liver cirrhosis.
• Substrate saturation of 11 beta-HSD2 contributes to mineralocorticoid excess in Cushing's syndrome and ectopic ACTH syndrome.
• HSD11B2 gene polymorphisms influence salt sensitivity and hypertension risk.
• Reduced placental 11 beta-HSD2 expression may link low birth weight to adult hypertension.

Conclusions:

• 11 beta-HSD2 is a critical regulator of sodium homeostasis and blood pressure.
• Dysregulation of 11 beta-HSD2 activity contributes to the pathophysiology of hypertension in various conditions.
• Understanding 11 beta-HSD2 function offers insights into hypertension prevention and treatment.