Endocrine Abstracts

Acetylation of DNA can result in gene silencing. In the thyroid such phenomena can lead to the loss of ability to accumulate radioiodide. The aim of this study was to examine the effects on the rat thyroid cell line FRTL-5 and human thyroid follicular cancer cell line FTC-133 of Trichostatin A (TSA), a histone deactylase inhibitor. A concentration of TSA was selected using MTT cell viability assays for use in uptake, efflux and expression studies. Cells were incubated with TSA...

Epigenetic phenomena such as methylation or acetylation of DNA can result in transcriptional inactivation and gene silencing. In the thyroid such phenomena can bring about the loss of ability to accumulate iodide as a result of methylation of CpG islands in human sodium iodide symporter (NIS) and Pendrin (PDS) DNA, limiting the ability to utilise radioiodide therapy. This study examines the effects of Trichostatin A (TSA) a histone deacetylase (HDAC) inhibitor on a rat thyroid...

Uptake of ingested iodide (I-) in the thyroid is achieved through an active transport system, the sodium iodide symporter (NIS). The gland has the ability to accumulate I- from the bloodstream by a factor of 20-40. Seaweeds, which in vivo bear the same relationship to seawater, as does the thyroid to the bloodstream, have a dramatically more efficient I- uptake system, accumulating I- from seawater by a factor of anything up to 1 mil...

The demonstration in extrathyroidal tissues of the sodium iodide symporter (NIS) has raised the possibility that 131I, commonly used as a therapeutic ablative agent in hyperthyroidism and thyroid cancer, might be applied in the treatment of tumours in other NIS expressing tissues such as human breast cancer. As thyroidal uptake of 131I is known to be inversely proportional to circulating stable I- concentration, the aim of this study was to determine how I- would effect such u...

Expression of the Sodium Iodide symporter (NIS) in the breast was thought to be restricted to lactation but recently have been shown in breast cancer and benign breast disease. CpG island methylation of the promoter region of NIS is known to decrease iodide uptake in the thyroid. No such information has been documented in the breast. The aim of this study was to investigate the effect of demethylating agents on iodide uptake in breast cancer cell lines MCF-7 (oestrogen (E) and...

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...