[Transcriptional repression of the TRH gene]

The synthesis and secretion of thyroid hormones (TH: T3, T4) must be strictly regulated. TH act on their own production via a negative feedback system. The synthesis of thyrotropin-releasing hormone (TRH), produced in the hypothalamus, and thyrotropin (TSH) in the pituitary is inhibited at the transcriptional level by TH. TRH and TSH stimulate production of TH. An outstanding, still open, question is the molecular basis of T3-dependent transcription repression of TRH and TSH genes. However, some regulatory components have been identified, with the b-TH receptor (TRb) playing a specific regulatory role (versus TRa) in the negative feedback effects of T3 on production of TRH and TSH. Moreover, the N-terminus of TRb is known to be a key element in this regulation. A hypothesis to explain this isoform specificity could be that TRb and TRa interact differentially with transcriptional comodulators. Thus, it is critical to characterize these comodulators and to analyse their contribution to the transcription regulation of TRH

Adiponectin expression and metabolic markers in obesity and Type 2 diabetes

International audienceBackground: Adiponectin has emerged over the last decade as a key adipokine linking obesity, insulin resistance, and Type 2 diabetes. However, the molecular mechanisms controlling adiponectin expression in adipose tissue are not fully elucidated. Furthermore, increasing evidence indicates that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays an important, and beneficial, role in modulating adiponectin expression. Aim: The aim of the present study was to assess the separate role of obesity and Type 2 diabetes in the relationship between endogenous PPAR-gamma signaling and adiponectin expression in subcutaneous adipose tissue. Subjects and methods: Enzyme-linked immunosorbent assay and real time quantitative PCR analysis were carried out in overweight, obese, and/or diabetic Tunisian patients who underwent an abdominal surgery. Results: These results collectively indicate that circulating levels of adiponectin were decreased in all over-weight, obese, and/or diabetic (p<0.001). However, the subcutaneous mRNA expression of adiponectin was reduced only in diabetics (p<0.01) but presents some discrepancies in obese individuals. Moreover, mRNA levels of adiponectin were positively correlated with levels of mRNA encoding PPAR gamma and its heterodimeric partner retinoid X receptor-alpha (RXR-alpha), in both obese and diabetic patients. Conclusion: Our study on Tunisian patients shows impaired regulation of circulating and mRNA adiponectin levels dependent of metabolic disorders in obesity and Type 2 diabetes. The data suggest that subcutaneous adipose tissue may play an important role in modulating adiponectin expression in diabetes and obesity. Moreover, adiponectin mRNA could be potentially regulated by endogenous PPAR gamma/RXR alpha-dependent pathways. (J. Endocrinol. Invest. 34: e16-e23, 2011) (C) 2011, Editrice Kurti