11β-Hydroxysteroid dehydrogenase

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[[Image:||thumb]] 11β-Hydroxysteroid dehydrogenase (11β-HSD) is an enzyme that plays a critical role in the biological process of steroid metabolism. This enzyme exists in two main isoforms, 11β-HSD1 and 11β-HSD2, each with distinct functions, tissue distributions, and implications for health and disease. The primary function of 11β-HSD is to catalyze the interconversion of cortisol and cortisone in humans, as well as their equivalents in other species, thus regulating the access of these hormones to their specific receptors.

11β-HSD1[edit | edit source]

11β-HSD1 predominantly acts as a reductase, converting cortisone to the active hormone cortisol. This isoform is widely expressed in liver, adipose tissue, central nervous system, and several other tissues. By generating active cortisol, 11β-HSD1 plays a key role in the local amplification of glucocorticoids, thereby influencing glucose metabolism, inflammation, and energy homeostasis. Dysregulation of 11β-HSD1 has been implicated in the development of obesity, type 2 diabetes, and metabolic syndrome, highlighting its potential as a target for therapeutic intervention.

11β-HSD2[edit | edit source]

In contrast, 11β-HSD2 functions primarily as a dehydrogenase, converting cortisol to its inactive form, cortisone. This isoform is highly expressed in the kidney, colon, and parts of the reproductive system, where it serves to protect the mineralocorticoid receptor from being activated by cortisol. This protection is crucial for the regulation of sodium retention, potassium excretion, and blood pressure. Loss of 11β-HSD2 activity, as seen in apparent mineralocorticoid excess (AME), leads to hypertension and hypokalemia due to excessive activation of mineralocorticoid receptors by cortisol.

Clinical Significance[edit | edit source]

The balance between 11β-HSD1 and 11β-HSD2 activity is essential for maintaining proper physiological levels of cortisol and cortisone, and disruptions in this balance can lead to various health issues. For example, excessive 11β-HSD1 activity can contribute to the development of metabolic disorders, while 11β-HSD2 deficiency can result in conditions like AME and gestational hypertension. Furthermore, the role of 11β-HSD enzymes in drug metabolism and their interaction with pharmacological agents is an area of ongoing research, with implications for the development of drugs targeting these enzymes.

Research and Therapeutic Approaches[edit | edit source]

Given the significant roles of 11β-HSD1 and 11β-HSD2 in health and disease, these enzymes are attractive targets for therapeutic intervention. Inhibitors of 11β-HSD1 are being explored for their potential to treat metabolic syndrome and type 2 diabetes, by reducing the local amplification of glucocorticoids in tissues. Conversely, inhibitors of 11β-HSD2 could potentially be used to treat conditions like AME by preventing the inappropriate activation of mineralocorticoid receptors.

Conclusion[edit | edit source]

11β-Hydroxysteroid dehydrogenase is a key enzyme in the metabolism of glucocorticoids, with significant implications for human health. Understanding the functions and regulation of its isoforms, 11β-HSD1 and 11β-HSD2, is crucial for elucidating the pathophysiology of metabolic and hypertensive disorders, and for the development of targeted therapies.


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Contributors: Prab R. Tumpati, MD