Cortisol Binding to Proteins in Plasma in the Human Neonate and Infant

Abstract

Extract: The binding of cortisol to plasma proteins was studied by a methodology allowing the determination of the apparent affinity constant (Ka) and the specific binding capacity (Ns) for transcortin in different blood compartments in normal pregnant women at term, in the umbilical cord blood, and in normal neonates and infants throughout the first year of life. Removal of endogenous steroids appeared to be necessary for these binding studies, especially in the cord plasma. Both an equilibrium dialysis and an adsorbent technique were used, inasmuch as it has been established that they yield similar results for corticosteroid-binding globulin (CBG) binding parameters. The high affinity binding of cortisol, attributed to transcortin, was found to have the highest capacity in plasma from pregnant subjects (Ns = 1.16 ± 0.19 × 10−6 M), whereas the fetal compartment (umbilical cord) exhibited low values (0.25 ± 0.03 × 10−6 M). Thus a physiologic barrier to the transplacental passage of transcortin resulted in a large concentration gradient in cortisol-specific binding sites between the fetal and maternal compartments. No significant differences were found for transcortin capacity between venous uterine plasma and peripheral plasma in three subjects studied during cesarean section. A possible physicochemical difference between maternal and fetal transcortin appeared unlikely, because in all blood compartments studied, the apparent affinity constant, Ka, was similar (5-8 × 108 M−1 at 4°), and the behavior of the specific cortisol binder in polyacrylamide gel electrophoresis was the same in all cases. After birth, although the transcortin Ka for cortisol was still in the same range, Ns remained low during the first month of life (0.23 ± 0.07 × 10−6 M); after which an increase toward normal adult values was seen, with a rather large variation between individuals from 2-12 months of age (mean 0.48 ± 0.10 × 10−6 M). Children above 1 year exhibited adult values for Ns (0.51 ± 0.03 × 10−6 M). Speculation: From the similarity of values found for transcortin Ka and electrophoretic behavior, the physicochemical properties of the glycoprotein cortisol binder are likely to be the same both in the maternal and fetal compartments, although final evidence of chemical identity is not available. Thus, the different binding capacity between these compartments might be attributed to a different concentration in circulating transcortin. This concentration gradient may play a role in the transplacental transfer of corticosteroids during pregnancy and would favor passage toward the maternal compartment. The low transcortin level in the neonatal period might be attributed to a low biosynthesis capacity of the liver in the neonate, although nothing is known about the clearance rate of transcortin in the neonatal period. The transcortin level increases toward adult values during the first year of life and this would suggest either a maturation of the liver biosynthesis enzymatic systems or a biosynthesis stimulation. A possible contribution of a pituitary factor might be suggested on the basis of experimental work in the rat, but the meaning of this increase in cortisol binding capacity in plasma remains to be elucidated.