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 non-developmentally 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.
Our evidence is consistent with two distinct regulatory pathways for TBG, one under direct negative control by the thyroid hormones, without GH mediation, and the other independent of the thyroid, but involving GH, possibly for its role in the control of carbohydrate metabolism. We have shown that TTR depends little on the thyroid and is regulated by pituitary factors in a complex way, since it is inhibited by Hx but also by treatment with GH. The divergent regulatory pathways of TBG and TTR may be important in the homeostasis of thyroid hormone bioavailability.
Journal of Endocrinology (1994) 142, 77–84
The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin.