Enhanced expression of transforming growth factor β1 in rat thyroid hyperplasia is thyrotropin induced and time dependent

Morosini, Pierpaolo; Taccaliti, Augusto; Arnaldi, Giorgio; Simonella, G.; Petrelli, Massimiliano; Mancini, Virginia; Montironi, R; Scarpelli, Marina; Diamanti, L.; Mantero, Franco

doi:10.1530/eje.0.1340373

Cited by 21 publications

(20 citation statements)

References 9 publications

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“…In rats injected with either TSH or with drugs that stimulate endogenous TSH secretion, such as methimazole or propylthiouracil (PTU), an increase in TGF-b1 production has been observed (28). In similar studies Logan et al (29) demonstrated an increase in TGF-b1 mRNA during goiter progression, while it decreased with goiter involution as it will be discussed below.…”

Section: Tsh Effectsmentioning

confidence: 94%

Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth

Pisarev

Thomasz

Juvenal

2009

Thyroid

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Transforming growth factor beta (TGF-beta) exists in nature as three isoforms. They exert their effects by binding to a type II receptor located at the cell membrane. The TGF-beta-type II receptor complex then recruits type I receptor, and this new complex stimulates the phosphorylation of Smads 2 and 3, which are subsequently transferred to the nucleus, where they regulate gene transcription. The thyroid gland expresses the TGF-beta1 gene mRNA and synthesizes the protein, which under physiologic conditions regulates thyroid growth and function. Different studies have demonstrated that TGF-beta1 inhibits cell proliferation and a number of functional parameters. These include cyclic adenosine monophosphate (AMP) formation, iodine uptake and organification, hormone secretion, and the expression of thyroglobulin, thyroid peroxidase, and Na(+)/I(-) symporter. The expression of the TGF-beta1 gene and protein may be stimulated by iodine under normal conditions. Since TGF-beta1 mimics some of the inhibitory actions of iodine, its participation in thyroid autoregulation has been proposed; however, this concept is still debated. In thyroid tumors, the inhibitory action of TGF-beta1 on cell proliferation is progressively lost as the tumor becomes more undifferentiated. The alterations in the signaling pathway of TGF-beta1 are not the same in tumors from different species. Even within the same species, such as the pig thyroid, the results may be different depending on whether monolayers or follicular suspensions are employed. The data suggest that it is not entirely possible to apply the results obtained in animal studies to normal or pathological human thyroid tissue. More studies are required to provide the information needed to develop treatments, based on targeting the signaling pathway of TGF-beta1, for undifferentiated thyroid cancer and other thyroid diseases.

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Section: Tsh Effectsmentioning

confidence: 94%

Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth

Pisarev

Thomasz

Juvenal

2009

Thyroid

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“…Some forms of epithelial hyperplasia are known to be associated with aberrant TGF 1-mediated growth control (Cui et al 1995, Roberts 1998, but clarification of the role for TGF 1 in MNTG is clouded by conflicting reports; Perlino et al (1996), for example, have reported a reduction in TGF 1 in hyperplastic, compared with normal, thyroid tissue, while a contemporary report (Morosini et al 1996) has recorded higher levels in recurrent goitre after thyroid surgery than in patients remaining in remission. Nevertheless, the evidence from the rat model implicating a critical role of TGF 1 in the limitation of iodide-deficiency goitre suggests that dysregulation of the stimulatory growth factor profile of the hyperplasia of MNTG may include a key change in TGF 1 bioavailability, which is clearly deserving of further study.…”

Section: Latent and Activated Forms Of Tgf And Their Receptorsmentioning

confidence: 99%

Growth factors and goitrogenesis

Bidey¹,

Hill²,

Eggo³

1999

Journal of Endocrinology

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By combining data from studies of multinodular non-toxic goitre (MNTG) with data from rat models of goitre induction and in vitro models, a map of the growth factors involved in goitrogenesis has been constructed. We have addressed the roles of the insulin-like growth factors, transforming growth factors, fibroblast growth factors, endothelins, etc. We hypothesise that an imbalance in the interactions between the various growth factor axes exists in MNTG which favours cell replication. Thyrotrophin, although not significantly elevated in MNTG, exerts critical effects through interactions with autocrine and paracrine factors and their receptors. Expansion of the thyroidal vascular bed through angiogenesis is closely co-ordinated with follicular cell expansion and folliculoneogenesis, and while the integrated paracrine actions of fibroblast growth factors, vascular endothelial growth factor and endothelin probably play central roles, additional, as yet elusive, factors are probably involved. The combination of in vitro and in vivo approaches, designed to address specific questions, will undoubtedly continue to prove invaluable in dissecting further the complex interactions that exist between these growth factors, their binding proteins and receptors in goitrogenesis.

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“…Thyrocytes from different species produce high amounts of TGF␤ in response to TSH (Contempre et al, 1996;Kolaja and Klaassen, 1998;Morosini et al, 1996;Pekary et al, 1995;Roger, 1996). VEGF, unlike GM-CSF and TGF␤, has been shown to inhibit the development of DC from hematopoietic progenitors (Gabrilovich et al, 1996(Gabrilovich et al, , 1998(Gabrilovich et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

Signaling from Epithelial to Dendritic Cells of the Thyroid Gland: Evidence for Thyrocyte-Derived Factors Controlling the Survival, Multiplication, and Endocytic Activity of Dendritic Cells

Croizet

Trouttet-Masson

Rabilloud

et al. 2001

Laboratory Investigation

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SUMMARY:Intrathyroidal dendritic cells (DC) isolated at the same time and then cultured with thyrocytes in the presence of thyrotropin (TSH) keep a phenotype of immature DC (Croizet et al, 2000). As DC from other sources are known to undergo a rapid maturation in vitro, we hypothesized that the maintenance of thyroid-derived DC in an immature state might be caused by thyrocytes-DC interactions. In this study, we investigated whether thyroid-derived DC could change their phenotype in response to TSH stimulation of thyrocytes.Over an 8-day period of culture, the population of DC increased 2-to 3-fold in the presence of TSH and decreased by more than 75% in the absence of TSH. The increase in the DC population was related to DC proliferation, whereas the reduction of the number of DC was secondary to a loss of cell-substrate adhesion and subsequent cell death. In the presence of TSH, DC acquired and maintained a high capacity for internalizing labeled ligands, expressed the mannose receptor, and exposed MHC class II molecules at the cell surface. On the contrary, DC cultured without TSH were devoid of endocytic activity and mannose receptor and, after 2 days, no longer exposed MHC class II molecules at the cell surface. Using conditioned media and enriched DC populations, we show that thyrocytes, in response to TSH, produce soluble factors capable of activating proliferation and endocytic activity of DC. Exogenous granulocyte/macrophage-colony stimulating factor and transforming growth factor-␤, known to be produced by thyrocytes, reproduced the effects of conditioned media.These data, giving evidence of a hormone-regulated signaling process between epithelial and dendritic cells in vitro, suggest that thyrocytes could promote the maintenance of a population of immature DC within the thyroid gland. (Lab Invest 2001, 81:1601-1613.

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Enhanced expression of transforming growth factor β1 in rat thyroid hyperplasia is thyrotropin induced and time dependent

Cited by 21 publications

References 9 publications

Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth

Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth

Growth factors and goitrogenesis

Signaling from Epithelial to Dendritic Cells of the Thyroid Gland: Evidence for Thyrocyte-Derived Factors Controlling the Survival, Multiplication, and Endocytic Activity of Dendritic Cells

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