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[11beta-hydroxysteroide dehydrogenases. Recent advances].

M-C Vantyghem1, S Marcelli-Tourvieille, F Defrance

  • 1Service d'endocrinologie et métabolisme, clinique d'endocrinologie Marc-Linquette, 6, rue du Professeur-Laguesse, CHRU de Lille, 59037 Lille cedex, France. mc-vantyghem@chru-lille.fr

Annales D'Endocrinologie
|March 21, 2007
PubMed
Summary
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11beta-hydroxysteroid dehydrogenase (11beta-OHSD) enzymes regulate cortisol metabolism. Understanding these enzymes, 11beta-OHSD types 1 and 2, offers new therapeutic strategies for metabolic syndrome and other conditions.

Area of Science:

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Context:

  • 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) enzymes are critical regulators of cortisol metabolism, influencing access to glucocorticoid and mineralocorticoid receptors.
  • Two main isoenzymes, 11beta-OHSD type 1 and type 2, have distinct tissue distributions and functions.
  • Type 2 11beta-OHSD, primarily in the kidney, inactivates cortisol to cortisone, protecting mineralocorticoid receptors.

Purpose:

  • To elucidate the distinct roles and mechanisms of 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) type 1 and type 2 enzymes.
  • To explore the pathological consequences of 11beta-OHSD dysfunction, including apparent mineralocorticoid excess and cortisone reductase deficiency.
  • To highlight the therapeutic potential of targeting 11beta-OHSD enzymes, particularly for metabolic syndrome.

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Summary:

  • 11beta-OHSD type 2 is a dehydrogenase that converts cortisol to cortisone, primarily in the kidney. Its deficiency, due to mutations or polymorphisms, causes apparent mineralocorticoid excess, leading to hypertension and hypokalemia.
  • 11beta-OHSD type 1 is a reductase, converting cortisone to cortisol, predominantly in the liver and adipose tissue. Functional defects are linked to polycystic ovaries and cortisone reductase deficiency.
  • Overactivity of 11beta-OHSD type 1 is associated with metabolic syndrome, osteoporosis, and glaucoma. Inhibitors of 11beta-OHSD are being developed as novel therapeutic agents.

Impact:

  • Elucidating the specific roles of 11beta-OHSD isoenzymes provides a deeper understanding of steroid hormone regulation.
  • Identifying genetic mutations and polymorphisms associated with 11beta-OHSD dysfunction clarifies the pathophysiology of various endocrine and metabolic disorders.
  • The development of 11beta-OHSD inhibitors represents a promising avenue for novel therapeutic interventions, particularly for metabolic syndrome and related conditions.