Influence of hypothyroidism on circulating concentrations and liver expression of IGF-binding proteins mRNA from neonatal and adult rats

Abstract

The aim of this work was to study the influence of the endocrine balance between thyroid hormones, insulin and growth hormone (GH) on the regulation of insulin-like growth factor binding proteins (IGFBPs), complementing a study previously reported for insulin-like growth factors (IGFs) in similar populations. Serum concentrations of IGFBPs-1 to -3 were assayed by Western ligand blot and their mRNA expression in the liver assayed by RNase protection assay in the hypothyroid populations: thyroidectomized and mercapto-1-methylimidazole (MMI)-treated neonates, and thyroidectomized adult rats at different periods after thyroidectomy. Serum concentrations of insulin, GH and IGF-I were increased in thyroidectomized neonates and decreased in the other populations. IGFBPs-1 and -2 increased 79% and 50% respectively in thyroidectomized neonatal rats compared with control at 15 days after thyroidectomy, whereas only IGFBP-2 increased (87%) in MMI-treated neonates, which had low serum insulin and GH compared with control on the same days. In thyroidectomized adult rats, IGFBPs-1 and -2 decreased 60% compared with controls on all days studied. Furthermore, when streptozotocin was administered to thyroidectomized neonates and insulin was given to thyroidectomized adult rats to restore insulin to control values in both groups, a differential regulation was found for IGFBPs-1 and -2. The transcriptionally induced decrease in IGFBP-3 (20-25% compared with control in neonates and 50% in adult rats), however, seemed to be regulated by GH and IGF-I. The similarity of changes in IGFBPs found in hypothyroid, undernourished and streptozotocin-induced diabetic neonatal rats suggests that the regulatory effect of insulin or GH on the IGFBPs requires the reduced biologically active thyroid hormone that is found in these three populations.

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

“…Hyperthyroidism increased the abundance of IGFBP1 in young chickens, which is in agreement with higher hepatic IGFBP1 expression found in neonatal thyroidectomized rats given thyroxine replacement (Ramos et al, 2001). Furthermore, insulin appears to mediate the effect of thyroid status on function of the IGF/IGFBP system (Ramos et al, 2002). Hyperthyroidism in chickens could reflect insulin resistance and diminished insulin signaling as suggested by reduced insulin receptor tyrosine kinase substrate (IRTKS, also known as BAI1-associated protein 2-like 1, BAIA2L1) transcript levels (Ruiz-Alcaraz et al, 2005).…”

Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction

“…Interestingly, the reduction in the concentration of GH can be attributed to the disruption of the activities of THs (Ahmed 2012), of the synthesis and release of growth hormone-releasing hormone (GH-RH), of the sensitivity of the pituitary gland to GH-RH, and of the transcription of the GH gene (Osfor et al 2013). It has also been shown that the effects of THs on IGF1 synthesis and secretion are mediated by insulin in neonatal hypothyroid rats (Ramos et al 2002). These findings are concomitant with those of the present study, where the depletion in the concentration of IGF1 was related to the alterations in the activities of THs and insulin that may delay growth.…”

Effect of Methylimidazole-Induced Hypothyroidism in a Model of Low Retinal Neovascular Incidence

“…MMI treatment is an established method of inducing thyroid dysfunction in rodent models. 18 lower doses of MMI or in MMI-treated control animals. However, based on the similar body weights of the untreated control and 40/15 groups, as well as between treated groups, it seems likely that MMI also effectively produced low thyroid function in the control rats and that the 40/15 procedure, per se, did not alter thyroid function.…”