Glucocorticoids induce corticosteroid-binding globulin biosynthesis by immature mouse liver and kidney.

Marked changes in mouse corticosteroid-binding globulin (CBG) gene expression in the liver and kidney occur postnatally. To study the influence of glucocorticoids on the initiation of mouse CBG biosynthesis in these tissues during the first two weeks after birth, we administered dexamethasone (0.5 microgram/g body wt/day) to 4- and 11-day-old pups for three days. This resulted in higher serum CBG and hepatic CBG mRNA levels in animals, irrespective of their ages. Higher relative amounts of CBG mRNA in the kidneys of 14-day-old pups after three days of dexamethasone treatment co-incided with higher amounts of intact and proteolytically cleaved CGB in their urine, and both are indicative of increased CGB production by the developing renal tubules. When an additional group of 11-day-old pups (n = 4) was treated with 0.25 microgram dexamethasone/g body weight per day for five days, this also resulted in significantly higher levels of serum CBG (P < 0.01), hepatic CBG mRNA (P < 0.01) and renal CBG mRNA (P < 0.05), compared to littermates treated with the oil vehicle alone. In contrast, serum CBG levels progressively decreased in adult female mice during five days of treatment with 0.5 microgram dexamethasone/g body weight per day. Taken together, these data indicate that glucocorticoids induce murine CBG gene expression in the immature liver and kidney, and support the concept that the effects of glucocorticoids on CBG gene expression are developmentally stage-specific.

Biological half-life and transfer of maternal corticosteroid-binding globulin to amniotic fluid in the rabbit.

Rabbit corticosteroid-binding globulin (CBG) from the serum of pregnant and nonpregnant females differs in terms of charge microheterogeneity, and both forms were, therefore, radiolabeled and injected iv into 23- to 27-day pregnant rabbits (n = 6) to assess their biological half-lives and possible transfer to the fetal compartment. After an initially rapid distribution phase, the serum half-lives of both forms of [125I]CBG were essentially identical (approximately 13 h) and did not vary at different gestational ages. There was also no difference in the transfer of either form of [125I]CBG from maternal to fetal compartments in any of the animals studied. Moreover, [125I]CBG showed no sign of degradation and retained its steroid-binding activity in fetal urine and amniotic fluid. Twenty-two hours after administration of [125I]CBG to rabbits (n = 2) at 23 days gestation, its mean level in fetal urine (7 cpm/microliter) and amniotic fluid (2.5 cpm/microliter) was much higher than that in fetal blood (0.6 cpm/microliter). More importantly, the specific activities of [125I]CBG in fetal urine and amniotic fluid were comparable to that in maternal serum, and approximately 2 orders of magnitude higher than that in fetal serum. Taken together, these results suggest that CBG in fetal urine and amniotic fluid is largely of maternal origin, and that maternal CBG crosses the fetal kidney preferentially.