Review Endocrine disruptors and other inhibitors of 11b-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition Jana Vitku a, *, Luboslav Starka a , Marie Bicikova a , Martin Hill a , Jiri Heracek b, c , Lucie Sosvorova a , Richard Hampl a a Institute of Endocrinology, Department of Steroids and Proteofactors, Prague, Czech Republic b Charles University, Third Faculty of Medicine, Department of Urology, Prague, Czech Republic c Faculty Hospital Kralovske Vinohrady, Department of Urology, Prague, Czech Republic A R T I C L E I N F O Article history: Received 26 February 2014 Received in revised form 9 July 2014 Accepted 19 July 2014 Available online xxx Keywords: 11b-hydroxysteroid dehydrogenase Inhibitor Endocrine disruptor Testis Colon Adipose tissue Brain Placenta A B S T R A C T 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 11b-hydroxysteroid dehydrogenase (11bHSD) 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 11bHSD 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 11bHSD 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 11bHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta. ã 2014 Elsevier Ltd. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2. 11b-hydroxysteroid dehydrogenase (11bHSD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.1. EDs and 11bHSD activities in testis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.2. EDs and 11bHSD activities in colon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.3. EDs and 11bHSD activities in adipose tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.4. EDs and 11bHSD activities in kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.5. EDs and 11bHSD activities in brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.6. EDs and 11bHSD activities in placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1. Introduction Since anthropogenic substances have been introduced to the environment, people have been continuously exposed to those chemicals. It was assumed that they do not have any biological effects, yet many of them might in fact disrupt the endocrine system. Evidence indicates the impact of these chemicals – endocrine * Correspondingauthor. Tel.: +420 224905238. E-mail address: jkubatova@endo.cz (J. Vitku). http://dx.doi.org/10.1016/j.jsbmb.2014.07.007 0960-0760/ ã 2014 Elsevier Ltd. All rights reserved. Journal of Steroid Biochemistry & Molecular Biology xxx (2014) xxx–xxx G Model SBMB 4226 No. of Pages 10 Please cite this article in press as: J. Vitku, et al., Endocrine disruptors and other inhibitors of 11b-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition, J. Steroid Biochem. Mol. Biol. (2014), http://dx.doi.org/10.1016/j.jsbmb.2014.07.007 Contents lists available at ScienceDirect Journal of Steroid Biochemistry & Molecular Biology journal homepage: www.else vie r.com/locate /jsbmb