Regulation of Transforming Growth Factor β1 Messenger Ribonucleic Acid Expression in Porcine Thyroid FolliclesIn vitroby Growth Factors, Iodine, or δ-Iodolactone

Abstract

Transforming growth factor beta 1 (TGF beta 1) is an autocrine growth factor for thyrocytes and is supposed to be the mediator of iodine-induced growth inhibition of thyroid epithelial cells, but this is still controversial. We further investigated this hypothesis using intact porcine thyroid follicles ex vivo in a three-dimensional culture system. In this culture system it has been shown previously that both iodide as well as delta-iodolactone, the putative iodocompound mediating thyroid cell proliferation, inhibit growth of these follicles. We measured the amount of TGF beta 1 mRNA expression in these follicles after treatment either with thyrotropin (TSH), epidermal growth factor (EGF), or transforming growth factor alpha (TGF alpha) for growth stimulation or with inorganic iodine or delta-iodolactone in concentrations known to inhibit growth. TGF beta 1-mRNA was detected by Northern blot analysis. The known major transcript of 2.5 kb was detected in a steady state level up to 48 hours in untreated thyroid follicles. EGF and TGF alpha (5 ng/mL each) enhanced TGF beta 1 mRNA about threefold within 4 and 8 hours. This increase of TGF beta 1 mRNA was slightly decreased by simultaneous incubation with delta-iodolactone (1 microM) or iodide (40 microM KI). In contrast, both TSH (1 mU/mL) and forskolin (16 microM) decreased TGF beta 1 mRNA expression to about 70%, and this effect was abolished when follicles were pretreated with iodide (40 microM KI) in a concentration known to inhibit TSH action on cyclic adenosine monophosphate (cAMP) formation and proliferation. Iodide or delta-iodolactone alone had no significant effect on basal TGF beta 1 mRNA expression. We conclude that the growth inhibitory effect of iodide as well as of delta-iodolactone is not mediated through TGF beta 1 in intact porcine thyroid follicles ex vivo. The stimulatory effect of EGF and TGF alpha on TGF beta 1 expression might be related to extracellular matrix modulation during proliferation.

Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules

“…This assumption is supported by findings of Ga¨rtner et al (1997), who could show a decreased expression of TGF-b1 mRNA after TSH stimulation of thyrocytes. Moreover, TGF-b1 has been shown to inhibit iodine uptake, iodine organification and thyroglobulin expression (Pang et al, 1992;Taton et al, 1993), as well as cell proliferation in different thyroid cell culture systems (Tsushima et al, 1988;Colletta et al, 1989;GrubeckLoebenstein et al, 1989;Depoortere et al, 2000).…”

Functional Localization of Proprotein-convertase Furin and its Substrate TGFβ in EGF Receptor-expressing Gastric Chief Cells

“…Co-localization of furin and its substrate TGFb was also observed in regenerating liver hepatocytes (Hoshino et al, 1997) and in laminar flow-loaded vascular endothelial cells (Negishi et al, 2001), and furin was shown to convert the TGFb precursor to its active form in the present study. These two proteins may be controlled by stimulants in a coordinated manner, and indeed, TGFb production was reportedly increased by EGF-R stimulation in enterocytes (Dignass and Podolsky, 1993) and thyrocytes (Gartner et al, 1997). Chief cells express a high level of EGF-R as reported previously , and EGF-R stimulation by TGFa increased the expression of furin and TGFb and promoted the production of a processed form of TGFb.…”

Rolle der totalen Thyreoidektomie im primären Therapiekonzept der benignen Knotenstruma

“…Mehrere Arbeitsgruppen zeigten in den vergangenen Jahren, dass das Wachstum benigner Knoten vom intrathyreoidalen Jodangebot abhängt und zusätzlich lokale Wachstumsfaktoren wie EGF, IGF-1 u. a einen Einfluss ausüben [7,8,11,13,38,39,40]. Das Belassen dieser wachstumsstimulierbaren Knoten im Schilddrüsenrestparenchym kann im weiteren Verlauf unabhängig von der TSH-Stimulation oder dem intrathyreoidalen Jodangebot zur Entwicklung einer Rezidivstruma führen.…”