Endocrine disruptors and other inhibitors of 11β-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition

J Steroid Biochem Mol Biol. 2016 Jan;155(Pt B):207-16. doi: 10.1016/j.jsbmb.2014.07.007. Epub 2014 Jul 24.

Abstract

Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.

Keywords: 11β-hydroxysteroid dehydrogenase; Adipose tissue; Brain; Colon; Endocrine disruptor; Inhibitor; Placenta; Testis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / enzymology
  • Brain / drug effects
  • Brain / enzymology
  • Colon / drug effects
  • Colon / enzymology
  • Diabetes Mellitus / chemically induced
  • Diabetes Mellitus / enzymology
  • Diabetes Mellitus / pathology
  • Endocrine Disruptors / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Glucocorticoids / metabolism
  • Humans
  • Male
  • Metabolic Syndrome / chemically induced
  • Metabolic Syndrome / enzymology
  • Metabolic Syndrome / pathology
  • Neoplasms / chemically induced
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Obesity / chemically induced
  • Obesity / enzymology
  • Obesity / pathology
  • Organ Specificity
  • Placenta / drug effects
  • Placenta / enzymology
  • Pregnancy
  • Testis / drug effects
  • Testis / enzymology

Substances

  • Endocrine Disruptors
  • Enzyme Inhibitors
  • Glucocorticoids
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2