Endocrine Abstracts

Epidemiological studies of postmenopausal women on oral oestrogen replacement therapy (ERT) show a reduction in the risk of developing colon carcinoma. Our previous study demonstrated that 17beta-oestradiol (E2) induced apoptosis in COLO205, a colonic cancer cell line. The aim of this study is to identify the genes important in the E2-induced apoptosis. cDNA array analysis 24h post E2 treatment showed a decrease in mRNA of erbB3 of 92%, K-RAS of 83% and p68TRK-T3 of 98% wherea...

When cultured in serum-free conditions, primary cultures of human thyroid cells display TSH-dependent iodide uptake and organification and iodide-dependent thyroid hormone synthesis. High iodide concentrations (>1 microM) inhibit thyroid hormone synthesis but iodide (0.1 microM) is obligatory for thyroid hormone secretion into the medium. We have performed in vitro studies examining the regulation of iodide transport and organification in cells preincubated in varying conce...

Because the sodium iodide symporter, NIS, may be artificially expressed in cells to introduce ablative doses of radioactive iodide, it may be of clinical use. NIS is normally found in the basolateral membrane of thyrocytes and its expression and activity are known to be regulated by TSH. We have used primary cultures of human thyrocytes to examine other regulators of NIS activity. NIS activity was measured as uptake of 125I into cells in the presence of the thyroper...

In vitro human thyroid follicular cells have been shown to secrete vascular endothelial growth factors (VEGFs). VEGFs transduce their effects by binding to their receptors, VEGFRs, leading to receptor phosphorylation and recruitment of downstream signalling molecules. Using RT-PCR we found that normal human thyroid follicular cells in culture express VEGFR-1, VEGFR-2 and VEGFR-3. Western blotting using antisera specific for phosphotyrosine at 1214 of the GRB2 SH2 bindin...

The plasminogen activator (PA) system plays a central role in biological processes that involve extracellular proteolysis including tissue remodelling, blood clotting, angiogenesis and metastases. The thyroid gland is highly vascular and undergoes extensive remodelling in goitre. We found that primary cultures of human thyroid follicular cells secrete large amounts of PAs (2.5-110 U per ml per day per 105 cells), both urokinase-like (uPA) and tissue-type (tPA), and ...

Preadipocytes differentiate into mature adipocytes when treated with insulin, T3, isobutylmethylxanthine and dexamethasone but the role of their autocrine factors in their survival and function has only recently been appreciated. We have examined the expression and role of autocrine FGF-2 during preadipocyte differentiation. Using human preadipocytes isolated from subcutaneous fat, we induced differentiation in differentiation medium with and without the insulin-sensitising dr...

Connective tissue growth factor (CTGF aka CCN2), is known to be up-regulated by transforming growth factor beta (TGF beta) and plays important roles in cell cycle control, growth, differentiation, cell adhesion, migration, angiogenesis and ECM production. CTGF is overexpressed in fibrotic disease e.g in kidney, lung, heart as well as in tumours. We have examined expression of CTGF in thyroid tissue because TGF beta is known be an autocrine factor, regulated by iodide. Immunohi...

The tyrosine kinase receptor, Tie-2, is expressed on endothelial cells where it has a role in angiogenesis in physiological and tumorigenic processes. We have shown that Tie-2 is also expressed on differentiated human thyroid follicular cells, and that its expression is increased in hyperplasia. This study aimed to elucidate the role of the Tie-2 axis in thyroid cells by examining regulation of Tie-2 expression in primary cultures of human thyroid follicular cells and the diff...

Human obesity is characterised by an increase in both the number of adipocytes and by an increase in their size, which is determined by adipogenesis. Adipogenesis can be induced in vitro in preadipocytes cultured in differentiation medium containing 3-isobutyl-1-methylxanthine, insulin, dexamethasone, and triiodothyronine but the signalling pathways important in adipogenesis are not well characterised. The p38 mitogen-activated protein kinase (MAPK) signalling pathway i...

We have recently shown that Tie-2, the receptor for the angiopoietins, is expressed on thyroid follicular cells. This angiogenic receptor was previously thought to be restricted to the endothelium where it influences the maturation of blood vessels. The role of Tie-2 in the growth, function and follicular architecture of thyroid cells is unknown. We have used primary cultures of human thyroid cells and the rat thyroid cell line, FRTL5 to examine the role of this axis. We have ...