Corticosteroid-binding globulin biosynthesis in the mouse liver and kidney during postnatal development

Abstract

Plasma corticosteroid-binding globulin (CBG) is produced by the liver, but low levels of CBG mRNA have been detected in other tissues, including the kidney. Glucocorticoids influence postnatal renal development in rodents, and CBG production in the kidney may influence the local bioavailability of glucocorticoids. We, therefore, used in situ hybridization and immunohistochemistry to define the sites of CBG biosynthesis during postnatal development and have found that the liver and kidney are major sites of CBG biosynthesis in the first weeks of life. Both CBG and its mRNA were undetectable in the neonatal liver, and only a weak hybridization signal for CBG mRNA was present in the 7-day-old mouse liver. In neonatal mice, the developing tubules of the kidney represent the most active site of CBG biosynthesis, and immunoreactive CBG was also detected in the same cells. By 7 days of age, CBG and its mRNA were colocalized to the proximal convoluted tubules of the juxtamedullary nephrons. The abundance of CBG mRNA in the liver increased from 10 days of age and was accompanied by similar increases in serum CBG until adult levels were reached by 4 weeks of age. In contrast, CBG mRNA in the kidney increased to a maximum during the third week of life, but was undetectable 3 weeks later. The CBG within the proximal convoluted tubules was located in secretory granules close to the luminal surface of the epithelial cells, suggesting that it is secreted into the tubular lumen. Western analysis revealed that marked proteolytic degradation of CBG occurs in the urine concurrently with an increase in CBG biosynthesis in the developing kidney. Thus, the liver is not the only site of CBG biosynthesis in the developing mouse, and CBG production by the epithelial cells of the proximal convoluted tubules may influence glucocorticoid-dependent maturation of the kidney tubules by a process that somehow involves proteolytic degradation.