Endocrine Abstracts

The PPARgamma is a ligand activated transcription factor that plays an important role in various biological processes including adipocyte differentiation and glucose homeostasis. Alternate promoter usage generates two receptor isoforms: PPARgamma2, containing 28 additional aminoterminal residues, is selectively expressed in adipose tissue whereas PPARgamma1 is more ubiquitously distributed. PPARgamma2 is strongly up regulated during adipogenesis, suggesting a specific role for...

Corepressors and coactivators mediate thyroid hormone receptor-dependent repression and transactivation of positively-regulated target genes respectively, but their role in negative regulation is not understood.A 4 years old boy was born at 31 weeks. He was jittery at birth, with neonatal respiratory distress. Childhood features included poor weight gain, heat intolerance, tachycardia and hyperactivity. Ongoing problems are low frequency hearing loss, po...

The superfamily of ~25 human selenoproteins includes antioxidant and oxidoreductase enzymes together with other proteins of unknown function. We describe a child with a multisystem disorder involving deficiencies of several selenoproteins, identified on the basis of abnormal thyroid function.A 3.6-year-old male was referred with elevated free thyroxine (FT4 – 44.4 pmol/l (N 12–22)), low free triiodothyronine (FT3 &#...

Hyperthyroid rats and humans exhibit increased energy expenditure and marked hyperphagia. Recent evidence has pointed that alterations of thermogenesis linked to hyperthyroidism are associated to dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear.Objective: The aim of our study was to assess if alterations in feeding in hyperthyroidism are asso...

The nuclear receptor PPARgamma is important for biological processes including adipogenesis and glucose homeostasis. In subjects with severe insulin resistance, we have previously reported two types of human PPARgamma gene defect: heterozygous, missense mutations (P467L, V290M) in the ligand binding domain (LBD) which inhibit wild type (WT) receptor action in a dominant negative manner by recruitment of transcriptional corepressors; or double heterozygosity for a frameshift/pr...

Introduction: Thyroid hormones act via receptors encoded by different genes (THRA and THRB) generating receptor subtypes (TRα1, TRβ1, TRβ2) with differing, tissue-specific expression. Resistance to Thyroid Hormone due to THRB defects is well recognised, but no THRA mutations have yet been reported. We describe the first case of human TRα-mediated thyroid hormone resistance due to a dominant negative THRA mutation.Results: A 6-year-old...