Thyroidology最新文献

Previous studies have shown that iodoarachidonates (IAs) prevent goiter production in rats. In the present studies we show that both IL-d and IL-w (IAs bearing the iodine atom at the positions 6 and 14, respectively), cause a significant involution of preformed goiter. This effect was evident when IAs were administered either orally or via i.p., although the first one required larger doses to obtain the same degree of inhibition. No changes were observed in serum protein, urea, cholesterol, cholinesterase, T3 or T4. In vitro studies with FRTL-5 cells showed that both IAs inhibit iodide and alpha-AIB uptake, as well as ATPase activity.

TSH, IGF-1 and cellular ras genes have been proposed to function in thyroid cell transformation. Using cultured follicular cells, we demonstrate that TSH, IGF-1 and microinjected activated ras protein individually stimulate DNA synthesis. TSH-stimulated pathways include Gs at the plasma membrane and cyclic AMP response elements in the nucleus. The pathways and nuclear targets of IGF-1 and ras action appear at least partially distinct from those used by TSH.

The mRNA for basic fibroblast growth factor has been detected in primary cultures of sheep thyroid cells. RNA species of 2.0 kb, 3.3 kb and 7.2 kb have been identified. The effects of this autocrine factor on the production of insulin-like growth factor binding proteins (IGFBPs) have been examined. bFGF enhanced the secretion of IGFBP-2 and, like epidermal growth factor (EGF) and the tumour promoting phorbol ester (TPA), induced the appearance of IGFBP-3. We conclude that bFGF is synthesized by sheep thyroid cells and has autocrine potential since it can regulate the secretion of other thyroid autocrine factors which, in turn, may regulate thyroid growth and function.

The mechanisms that generate the intercellular heterogeneity of functional and proliferation responses in a tissue are generally unknown. In thyroid gland, this heterogeneity is peculiarly marked and it was suggested that it could result from the coexistence of (epi)genetically different subpopulations of thyrocytes. As summarized in this short review, qualitative or quantitative intercellular heterogeneities have been found at each levels of our "in situ" investigations of morphological, differentiation and proliferative responses of unselected dog thyrocytes in primary culture. These different heterogeneities are unrelated at the individual cell level, which does not indicate the coexistence in thyroid of cell subpopulations stably expressing special properties. Nevertheless, using a double labeling methodology that allows to trace the proliferative behavior of some cells, we show how cell division may stably affect further proliferation responses and how a local synchrony of the dividing cells can result in a stable heterogeneity with a regional, patchy pattern, which resembles the one characterizing multinodular goiter.

In the present investigation we show data from our studies of anaplastic human thyroid carcinoma cell lines. The cell lines employed in the study were HTh 7, HTh 74, C 643 and SW 1736, all derived from tumours diagnosed as anaplastic thyroid carcinomas. Northern blot analysis with four different thyroid specific cDNA probes showed a varying pattern of expression. Thyroglobulin mRNA was found in three of the carcinoma cell lines, although the signal was very weak compared to the expression in tissue from a toxic goitre, used as positive control. Interestingly, two of the cell lines expressed the receptor for thyrotropin, but none of them contained thyroperoxidase mRNA. Three of the cell lines expressed mRNA for receptors platelet-derived growth factor, PDGFR-alpha and/or PDGFR-beta type. Messenger RNA of a thyroid specific transcription factor, TTF-1, known to regulate the normal function of thyrocytes, was found in the toxic goitre but not in the anaplastic thyroid carcinoma cell lines. Lack of expression of TTF-1 might the immediate cause of the anaplastic phenotype, considering the possibility that TTF-1 functions as a master regulatory gene in thyroid cell differentiation.

The reconstruction of the thyroid follicle was studied in vitro using the porcine thyroid cell line ATHOS. When performed monolayers of ATHOS cells grown after more than 50 passages are cultured in a sandwich of collagen in the presence of thyrotropin (10 mU/ml), figures resembling follicles are observed under light microscopy. By electron microscopy cells appear correctly polarized, microvilli facing follicle lumina. These histiotypical figures that mimic the thyroid architecture are maintained 4-5 weeks.

Thyrotropin stimulates the growth and proliferation of thyroid cells in vivo. Starting in the 1970, we have progressively shown that these effects could be reproduced in vitro in dog thyroid cells in primary culture. They are accompanied by the expression of differentiation. All the effects of thyrotropin are mediated by the cyclic AMP cascade. The best argument that this concept applies in vivo is the generation of hyperfunctioning adenoma involving the whole gland in transgenic mice expressing the constitutively active adenosine A2 receptor in the thyroid.

The mechanism involved in the neoformation of thyroid follicles is poorly understood. In the present study, whole porcine thyroid follicles were cultured as "miniorgans", embedded within collagen gels. Incubation was performed up to 4 days with or without EGF (10 ng/ml) and TSH (2 mU/ml). A single dose of 3H-thymidine was added at the start of the experiments in some cases. Light microscopy and autoradiography was performed. EGF induced a dramatic migration of follicles cells; these were seen to back out from the mother follicle and formed microfollicles with normal polarity including microvilli at the apical border. As evident from the analysis of 3H-thymidine incorporation, most microfollicles were comprised of newly divided cells. The results infer a new mechanism for the neoformation of follicles in the thyroid.

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.