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Statins and Downstream Inhibitors of the Isoprenylation Pathway Increase Type 2 Iodothyronine Deiodinase Activity
Endocrinology, 07/03/2012
Clinical Article
Miller BT et al. – The data indicate that statins and downstream inhibitors of the isoprenylation pathway may increase thyroid signaling via stimulation of D2 activity.
Methods- The authors report that statins and prenyl transferase inhibitors actually increase D2 activity in cells with endogenous D2 expression.
- Although the authors confirmed that lovastatin (LVS) decreases the activity of transiently expressed D2 in HEK–293 cells, the prenyl transferase inhibitors increase activity in this system as well.
- LVS treatment increases endogenous Dio2 mRNA in MSTO–211H cells but does not alter transiently expressed Dio2 mRNA in HEK–293 cells.
- The prenyl transferase inhibitors do not increase Dio2 mRNA in either system, indicating that a posttranscriptional mechanism must exist.
- Cotreatment with LVS or the prenyl transferase inhibitors with the proteasome inhibitor MG–132 did not lead to additive increases in D2 activity, indirectly implicating the ubiquitin–proteasomal system in the mechanism.
- Finally, C57BL/6J mice treated with LVS or farnesyl transferase inhibitor–277 for 24 h exhibited increased D2 activity in their brown adipose tissue.