Postnatal Development of Corticosteroid-Binding Globulin: Effects of Thyroxine*

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Abstract
The aim of this study was to examine the temporal and dose characteristics of the corticosteroid-binding globulin (CBG) response to T4 and to determine whether this response is due to stimulation of hepatic biosynthesis of CBG. When n-propylthiouracil (PTU)-induced hypothyroid pups were given a single injection of T4 (0.1 μug/g BW) on postnatal day 5, 6, or 7, only pups treated on day 7 showed a significant increase in CBG. In a T4 dose-response study conducted with 5- and 8- day-old pups, older pups exhibited maximum CBG concentrations (Rmax) which were 2.5-fold higher than those of younger pups. The D½ (dose required to elicit half the maximum response) values were similar at both ages. The effect of T4 withdrawal on serum CBG was also studied in PTU-treated pups. T4 injection on postnatal days 5–19 resulted in a progressive rise in CBG. In pups treated with T4 on days 5–9 and then withdrawn from treatment through day 20, serum CBG showed no further increase but was maintained at an elevated level. Using a liver slice system to assess CBG production in vitro, livers from 14-day-old hyperthyroid pups produced 4.77 ng corticosterone bound/g liver, while livers from euthyroid pups produced no CBG. We conclude: 1) the response of CBG to T4 is a function of the age of the animal; between days 5 and 8 this is due to increased Rmax without any change in sensitivity to T4 (D½); 2) T4 is required not only to initiate but also to sustain the developmental increase in CBG; and 3) T4 elicits an increase in circulating CBG by stimulating its synthesis.