Kinetics of radiolabeled adrenocorticotropin hormone in infant and weanling rats.

Unlike the adult animal, the developing rat has a diminished ability to activate and inhibit the hypothalamic pituitary adrenal axis. In general, a gradual ACTH and corticosterone response to stressors appear after postnatal day 10 and is well established to adult level by weaning age. Although at this age the peak ACTH level is comparable to that of the adult, ACTH levels remain elevated for a longer period of time. The purpose of this study was to investigate the possibility that ACTH metabolism can, in part, explain this prolonged ACTH elevation after a challenge. The plasma half life of disappearance (t1/2, the apparent volume of distribution and metabolic clearance rate (MCR) were determined after injection of a tracer dose of 3-I125-Iodotyrosyl23 ACTH1-39 in rats at 14 and 25 days of age. An adult animal group (65 days old) was used for comparison. The t1/2 for ACTH decreases with age (14 day old = 7.47 +/- 0.9 min; 25 day old = 6.48 +/- 0.4 min; adult = 4.46 +/- 0.2 min) while the volume of distribution remains constant. The MCR is also decreased in the young animals (14 day old = 1.5 +/- 0.19 min; 25 day old = 1.6 +/- 0.18 min; adult = 3.0 +/- 0.56 min). For the first time, it is established that the young animals require longer to clear ACTH from an equivalent volume of blood when compared to the adult. Thus, the kinetic properties of ACTH are different in the developing animal and this partly explains the prolonged ACTH elevation observed after stress challenges.