Endocrine Abstracts

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...

Glucocorticoids (GC) are potent anti-inflammatory compounds, acting mainly through the glucocorticoid receptor (GR). GC therapy, however, has debilitating side-effects, necessitating safer new alternative therapies. The natural GC metabolite 5α-Tetrahydrocorticosterone (5αTHB) is anti-inflammatory in vivo in mice, but with fewer side-effects. Its mechanism of action is unknown, and here we test signalling via GR and the mineralocorticoid receptor (MR). 5&#94...

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...