11 beta-Hydroxysteroid dehydrogenase

Area of Science:

• Biochemistry
• Endocrinology
• Molecular Biology

Background:

• Mammalian tissues possess two 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes, 11 beta-HSD1 and 11 beta-HSD2, which interconvert active corticosteroids and inactive metabolites.
• These isozymes are distinct gene products with low homology (14%) and exhibit different physiological roles, regulatory mechanisms, and tissue distributions.

Purpose of the Study:

• To review the enzymology, molecular biology, distribution, regulation, and function of 11 beta-HSD isozymes.
• To highlight the clinical implications of altered 11 beta-HSD expression.

Main Methods:

• Literature review of enzymology and molecular biology studies.
• Analysis of physiological roles and tissue distribution of 11 beta-HSD isozymes.
• Examination of clinical consequences related to mutations and altered expression.

Main Results:

• 11 beta-HSD2 acts as a dehydrogenase, protecting mineralocorticoid receptors and preventing glucocorticoid excess; mutations cause apparent mineralocorticoid excess syndrome and hypertension.
• 11 beta-HSD1 primarily functions as a reductase in vivo, enhancing glucocorticoid action in target tissues like the liver and adipose tissue.
• 11 beta-HSD has evolved from a peripheral metabolism enzyme to a critical pre-receptor signaling pathway.

Conclusions:

• The distinct functions of 11 beta-HSD1 and 11 beta-HSD2 are crucial for regulating corticosteroid hormone action and maintaining physiological balance.
• Dysregulation of 11 beta-HSD isozymes has significant clinical consequences, particularly in hypertension and metabolic disorders.
• Understanding 11 beta-HSD isozymes offers insights into corticosteroid signaling and potential therapeutic targets.