Selective activators of thyroid hormone receptors.
An excess of thyroid hormone (TH) leads to a mix of deleterious (increased heart rate, muscle wasting and osteoporosis) and beneficial effects (reduced serum cholesterol and lipoprotein A and weight loss). All of these actions are mediated by nuclear thyroid hormone receptors (TRs), however, genetic evidence suggests that different TR isoforms do not contribute equally to individual TH effects. Thus, TR isoform selective activators could mimic the beneficial aspects of TH excess while avoiding the harmful effects. This article reviews new selective TR activators, their mechanism of action (they work by targeting the TR-beta isoform) and their actions in animal models. It is clear that these compounds represent a promising new avenue for the treatment of lipid disorders and obesity.
Webb
Paul
P
Diabetes Center and School of Medicine, University of California-San Francisco, San Francisco, CA 94143-0540, USA. webbp@itsa.ucsf.edu
D000818:Animals; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones