Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone

Abstract

We have investigated the role of the thyroid compared with the hypophysis in the regulation of the two saturable thyroid hormone carriers of rat serum, thyroxine-binding globulin (TBG) and transthyretin (TTR). We examined, at serum and hepatic mRNA level, the responses of TBG and TTR to thyroidectomy (Tx), hypophysectomy (Hx) and replacement treatments with tri-iodothyronine (T3) or/and GH, both hormones which are depleted when the thyroid or hypophysis are removed. The studies were performed on male rats at the age of 8 weeks, when the developmentally regulated TBG becomes undetectable after its transient postnatal rise, while the nondevelopmentally regulated TTR presents its normal, age-independent level of expression. Tx-induced TBG re-expression was completely reversed by T3 replacement and unresponsive to GH replacement. TTR in the serum, on the other hand, was not affected by Tx or T3 replacement, moderately reduced by Tx in terms of the amount of mRNA, and markedly reduced by GH replacement. GH treatment, moreover, inhibited the expression of TTR in euthyroid controls. Hx, like Tx, induced TBG re-expression, an effect efficiently antagonized by T3 replacement. However, TBG synthesis was higher in Hx than in Tx rats and less effectively antagonized by T3 replacement. Most unexpectedly, GH induced a dramatic further increase in TBG synthesis, and the TBG synthesized in the GH-replaced Hx rats was entirely resistant to down-regulation by T3 replacement. TTR was markedly decreased at both serum and hepatic levels by Hx, unaffected by T3 and further decreased by GH replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

“…In rat experiments, thyroidectomy induced TBG reexpression which was completely reversed by T3 replacement and unresponsive to GH replacement, indicating a direct negative control by thyroid hormones [24]. The concomitant decrease of TBG and thyroid hormones in the Ox group indicates that the TBG downregulation was not mediated by the thyroid hormones.…”

“…Hypophysectomy induced also TBG reexpression which was less effectively antagonized by T3. The authors hypothesized that there is an alternative pathway for TBG regulation, independent of the thyroid, but involving GH possibly for its role in the control of carbohydrate metabolism [24]. Davidson described an anti-insulinic effect of hypophysectomy [21].…”

The role of type I and type II 5′ deiodinases on hexachlorobenzene-induced alteration of the hormonal thyroid status

“…Collectively, these three proteins transport more than 95% of T 3 and T 4 hormones (Barlow, 1997;Bartalena and Robbins, 1992). In rats, a significant difference is that TBG is not found between 2 and 7 months, the age range typically used in basic toxicology studies (Vranckx et al, 1994). In adult rats, T 4 and T 3 are bound to the low affinity carriers albumin and TTR.…”

Influence of thyroidectomy on thyroxine metabolism and turnover rate in rats

“…Changes in urinary excretion of T 4 and deiodination of T 4 to rT 3 following Tx warrant further investigation. In addition to these changes in T 4 metabolism, Vranckx et al (1994) reported that Tx induces expression of T 4 -binding globulin (TBG), and suggested that regulation of TBG may thus be important for thyroid hormone homeostasis. Further study is required to completely determine the mechanisms of thyroid hormone homeostasis after Tx.…”