Tri-iodothyronine increases insulin-like growth factor binding protein-4 expression in rat hepatocytes

Demori, Ilaria; Bottazzi, C; Voci, Adriana; Gallo, Gabriella; Jg, Scharf; Fugassa, E

doi:10.1677/joe.0.1540155

Cited by 22 publications

(29 citation statements)

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“…A similar T 3 -increased IGFBP-4 expression has been recently reported in cultured rat hepatocytes and is consistent with in vivo experiments demonstrating an increase in serum IGFBP-4 levels in T 3 -treated rats (36). In addition, previous studies showed the specific stimulation of IGFBP-4 expression by T 3 and/or RA in human breast cancer cell lines (49) and mouse osteoblasts (35).…”

Section: Discussionsupporting

confidence: 90%

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells

Bottazzi

Demori

et al. 1999

European Journal of Endocrinology

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A large body of evidence suggests the existence of an intratesticular IGF system complete with ligands, receptors and binding proteins (IGFBPs); the aim of the present study was to evaluate tri-iodothyronine (T 3 ) and retinoic acid (RA) effects on IGFBP production by Sertoli cells. A significant dose-dependent increase in IGFBP-4 mRNA levels was observed in Sertoli cells cultured in the presence of physiological concentrations of T 3 or RA. This response was inhibited by cycloheximide, indicating that de novo protein synthesis is required, as well as by actinomycin D, suggesting that the increase in mRNA levels requires transcriptional activation. As shown by ligand blot assays the stimulatory effects of both agents on IGFBP-4 mRNA expression appears to be consistent with an enhanced synthesis and secretion of IGFBP-4, thus suggesting that the transcriptional response is transduced to the protein level. Our data establish an important direct role for T 3 and RA in regulating IGFBP-4 expression and consequently IGF activity at the testis level.

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Section: Discussionsupporting

confidence: 90%

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells

Bottazzi

Demori

et al. 1999

European Journal of Endocrinology

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“…We have recently demonstrated a tri-iodothyronine (T 3 )-induced increase in IGFBP-4 expression in a rat hepatocyte model, in total agreement with the in vivo effects of thyroid hormone withdrawal from or administration to the rats (Demori et al 1997). In the same experiments, we were unable to obtain evidence of an effect of T 3 on IGFBP-2 expression, because of the barely detectable level of IGFBP-2 message in cultured hepatocytes from adult rats.…”

Section: Introductionmentioning

confidence: 55%

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Demori

Bottazzi²,

Fugassa³

1999

Journal of Endocrinology

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Previous evidence suggests the existence of a thyroid hormone-IGF axis in the liver and changes in hepatic insulin-like growth factor binding protein (IGFBP) expression in rats with altered thyroid status have been previously reported.The aim of this study was to check if the higher IGFBP-2 mRNA levels observed in liver of hypothyroid rats could be due to a direct effect of thyroid hormone on the IGFBP-2 gene. In our experiments, cultured hepatocytes isolated from normal and hypothyroid adult rats were used. Northern blot analysis revealed barely detectable IGFBP-2 mRNA in normal rat hepatocytes, but easily detectable signal in hypothyroid rat cells. Therefore, the effect of tri-iodothyronine (T 3 ) was investigated using cultured hepatocytes from hypothyroid rats as an in vitro model.The IGFBP-2 message was increased in a dosedependent manner in hepatocytes cultured for 12-24 h in the presence of T 3 . A similar increase occurred in accumulation of IGFBP-2 in the culture medium, as measured by RIA. The effect of T 3 on IGFBP-2 transcript levels appeared to consist of enhanced gene transcription and was independent of ongoing protein synthesis, but it was completely abolished by the incubation of hepatocytes with insulin. The latter result confirmed the dominant role of insulin in regulating IGFBP-2 expression by cultured hepatocytes.In vivo experiments confirmed an increase in hepatic IGFBP-2 mRNA and serum IGFBP-2 levels in hypothyroid rats and demonstrated, in addition, a significant increase in these measures in T 3 -treated rats.Taken together, our in vitro and in vivo results support a role for a thyroid hormone-IGF axis in the liver and suggest that other factors, such as insulin, interact in vivo with thryoid hormone in regulating hepatic IGFBP-2 expression.

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“…75 mM, FFAs) for different periods of time (1, 3, and 6 h). After choosing the optimal conditions of exposure to FFAs, FFA-treated hepatocytes were incubated in the absence (FFAs) or in the presence of T 2 or T 3 at different concentrations (nominal concentrations ranging from 10 K7 to 10 K5 M) for 24 h (Demori et al 1997). Both iodothyronines were added from stock solutions (10 K3 M in 50 mM NaOH).…”

Section: Cell Culturementioning

confidence: 99%

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-L-diiodothyronine (T 2 ), as well as 3,3 0 ,5-L-triiodothyronine (T 3 ), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T 2 and T 3 to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRa1 and TRb1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T 2 or T 3 for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-a, -g, -d) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O 2 consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARg mRNA expression, and a decrease in PPARd and SCD1 mRNA expression. The addition of T 2 or T 3 to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARa, PPARg, and AOX expression; iii) increase in PPARd expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T 2 and T 3 are not mediated by TRs.

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Tri-iodothyronine increases insulin-like growth factor binding protein-4 expression in rat hepatocytes

Cited by 22 publications

References 0 publications

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

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