Kinetics of circulating corticosterone in infant rats

Corticosterone plays an important role in the regulation of postnatal development in the rat. Basal concentrations of plasma corticosterone increase markedly during the 3rd wk of life. To date, however, the physiologic bases of this increase have remained unclear. To understand the determinants of circulating concentrations of corticosterone during this period, the plasma half-life of disappearance at steady state (t1/2), the apparent volume of distribution, and metabolic clearance rate were determined after injection of a tracer dose of 3H-corticosterone in rats at 12, 16, and 22 days of age. The t1/2 for total plasma corticosterone decreased with increasing age. The volume of distribution decreased even more steeply and, consequently, the MCR displayed a highly significant decline between 12 and 22 days of age. As plasma concentrations of corticosteroid-binding globulin are known to increase markedly during this period, the t1/2 of protein-bound corticosterone was measured and that of free corticosterone was computed. At all ages the t1/2 of bound corticosterone was less than that of free corticosterone. Protein binding of the injected 3H-corticosterone increased significantly with development. Thus, increased binding of corticosterone is associated with decreased t1/2. The increasing association of corticosterone with corticosteroid-binding globulin during this developmental period is the most likely explanation for the steep decline of volume of distribution and thus of the metabolic clearance rate for corticosterone. The latter provides, for the first time, an understanding of the basis of the developmental increase in plasma concentrations of corticosterone.