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In vitro studies of the control and activation of thyroidal transforming growth factor-beta1
Başlık:
In vitro studies of the control and activation of thyroidal transforming growth factor-beta1
Yazar:
Cowin, Alison J., author.
ISBN:
9780438084742
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (339 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Non toxic goitre is among the most common pathological condition of the thyroid gland, and is characterised by localised or diffuse hyperplasia of follicular cells. Transforming growth factor-beta1 (TGF- beta1) is an established regulator of epithelial cell proliferation, and has previously been shown to function as an autocrine growth inhibitor of thyroid follicular cells. The present study has investigated the mechanisms of thyroidal TGF-beta1 expression, and has considered whether alterations in thyroidal TGF-beta1 availability may contribute to the hyperplasia of simple sporadic goitre. Thyroid follicular cells from normal porcine thyroid glands, and sporadic nontoxic goitre tissue, were maintained as monolayer cultures. RNA extracts from both cell types were found to contain a 2.5Kb mRNA transcript hybridising to a cDNA probe for human TGF-beta1, which was increased in cells exposed to iodide. Other isoforms of TGF-B (TGF-beta2 and TGF-beta3) were not detected. No differences were seen between the responses of TGF-beta1 mRNA to iodide in normal and goitrous cells, and in both cell types the response was abolished by the thionamide drug, methimazole (MMI), an inhibitor of intracellular iodide processing, iodide also reduced thyroid cell DNA synthesis, which was also prevented by MMI treatment. The inhibitory actions of organic iodine on thyroid cell growth were reversed by TGF-beta1 immunoadsorption, although the effect was less-marked on goitrous human cell growth than on that of normal porcine cells. Evidence for thyroidal TGF-beta1 peptide release was obtained by exposing monolayers of the foetal mink lung cell line, Mv1Lu, to thyroid cell-conditioned medium. After heat treatment to simultaneously activate endogenous TGF-beta1 and inactivate growth-stimulating peptides, medium conditioned by normal or goitrous thyroid cells reduced the basal level of [methyl 3H] thymidine incorporation into Mv1Lu cultures. Substantially greater inhibition was found with medium from iodide treated thyroid cells, which was abolished by TGF-beta1 immunoadsorption. Thus, at a peptide, as well as an mRNA level, thyroidal TGF-beta1 production was up-regulated by iodide metabolites, in both normal and goitrous thyroid follicular cells. Certain of the thyroid growth-regulatory actions of iodide are thought to be mediated by iodolactone derivatives of essential fatty acids. Of a series of such compounds tested on normal and goitrous thyroid cells, only the 8-iodolactone of eicosapentaenoic acid (EPA) reduced thyroid cell growth, and this was unaffected by TGF-beta1 immunoadsorption. This, and the finding that Mv1 Lu cell growth was suppressed by medium from EPA-treated thyroid cells suggests that iodide-dependent up-regulation of thyroidal TGF-B1 synthesis may involve an iodocompound other than EPA. TGF-beta1 synthesis in porcine thyroid cells was responsive to TSH and IGF-I, and although TGF-beta1 immunoadsorption of TSH or IGF-I treated cultures had no effect on [methyl 3H]-thymidine incorporation, immunoadsorption of cultures exposed to both TSH and IGF-I led to an increase in [methyl 3H]-thymidine incorporation that exceeded that seen after similar treatment of cultures exposed to TSH or IGF-I alone. The finding that TGF-beta1 mRNA in porcine thyroid cells was enhanced by exposure to recombinant TGF-beta1 confirmed that, as in other epithelial cells, thyroidal TGF-beta1 may upregulate its own synthesis through autocrine feedback. High doses of EGF also stimulated thyroidal TGF-beta1 production, and the inhibition of [methyl 3H] thymidine incorporation under such conditions was abolished by TGF-beta1 immunoadsorption.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686909.1) | 686909-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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