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)

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Abstract. We describe the preparation of monospecific antisera against a thyroxine-binding globulin partially purified from immature rat sera by affinity chromatography on thyroxine-Sepharose. The antisera are used for the rocket immunoelectrophoresis assay of rat thyroxinebinding globulin and also, owing to their partial crossreactivity with mouse thyroxine-binding globulin, for the quantitation of this serum binding protein in the mouse. The thyroxine-binding globulin is measured in developing rats and in sexually mature male and female rats and mice. The results of the ontogenetic study confirm the postnatal surge of serum thyroxine-binding globulin levels, formerly demonstrated with binding techniques. They allow further to define the correlations, dependent on age, of the immunoquantitated thyroxine-binding globulin and transthyretin levels with the abilities of the sera to bind thyroxine. In sexually mature rats and mice we demonstrate an opposite sexdependence of thyroxine-binding globulin levels, characterized by increased levels of the protein in the female rats versus increased levels of the protein in the male mice. This is the first report of immunological quantitation of rat and mouse thyroxine-binding globulins.

Thyroxine-binding globulin, the highest affinity thyroid hormone binder of rat serum, was studied during 28 days of dietary protein restriction (6% protein vs 18% protein in isocaloric control diet) or energy restriction (60% intake of control diet). Studies were performed on male rats aged four weeks at the beginning of experiments: the animals had reached the ontogenic stage when the thyroxine\x=req-\ binding globulin had declined, after its high postnatal surge, to undetectable levels. Short-term administration (seven days) of one or the other restricted diet similarly induced resynthesis of the protein. Its serum concentrations reached 26\p=n-\46% of those measured in eight-day pups (peak of the neonatal surge) and its liver mRNAs showed corresponding enhanced signals. Serum T4 binding activities were increased, although concomitantly transthyretin, second specific T4 carrier of the rat serum, decreased markedly (65\p=n-\75% of controls) in response to the dietary restrictions. Longer-term diet administration (14 or 28 days) resulted in the further increase of the thyroxine-binding globulin in the protein-restricted rats, in contrast to its decline and eventual disappearance in the energy-restricted animals. Protein restriction was associated with increased total and free T3 serum concentrations, in contrast to energy restriction which little affected these parameters. These studies reveal rat thyroxine\x=req-\ binding globulin as a positive (increasing), highly sensitive reactant of malnutrition, able to discriminate between energy deficiency and composition dysequilibrium of diets. They suggest that up\ x=r eq-\ regulation of its synthesis in the two dietary models involves differential mechanisms.