Half-life of Plasma Corticosterone During Development

The metabolic half-life of corticosterone in rats of different ages was studied. Halflife was determined by the rate of disappearance from the circulation of radioactive corticosterone following intracardiac or intravenous injection of the labeled hormone. There is a progressive decrease in half-life from about 120 min in the new born rat to about 20 min at 40 days of age (Endocrinology 89: 284, 1971) D the early post-natal period in the rat the secretion of ACTH generally does not occur in response to a wide range of physiological insults. It is doubtful whether the small, but statistically significant, increase that does occur in response to certain severe stresses is of physiological significance. The basis for this neonatal neuroendocrine quiescent period is unclear, although the work of Bartova (1) indicates that a deficiency of hypothalamic CRF may be a contributory factor. We have earlier suggested that immaturity of the ACTH secretion mechanism may provide for the later expression of immunological competence (2) and normal CNS functional development (3, 4). In contrast to immaturity of ACTH secretion in response to external (environmental) stresses, the steroid feedback mechanism is functioning during the first post-natal week as judged by adrenal atrophy caused by exogenous corticoid administration and compensatory adrenal hypertrophy (5, 6). The apparent increased sensitivity of this feedback mechanism to exogenous corticoids (7) could be due to a longer effective persistence of the hormone in the circulation and/or its greater accessibility to CNS sites involved in feedback regulation. This brief report describes the maturation of the metabolic half-life of corticosterone in the rat. Materials and Methods Sprague-Dawley derived rats bred in this laboratory were used in all experiments. Corticosterone-H (Amersham-Searle TRK-141, specific activity 31.7 Ci/mmole) in ethanol was evaporated under nitrogen and resuspended in 10 % ethanol for injection. Injections into the unanesthetized infant rat, younger than 15 days of age, were done directly into the heart by a technique developed in this laboratory (to be published). Rats older than 16 days were males and received the hormone via Received August 11, 1970. Supported in part by USPHS Grant HD04369. the tail vein. All animals received 2 /iCi/10 g body wt in a volume of 2 ^1/g body wt. Three to 10 animals were used for each age group. Tail or toe blood was generally taken at 2, 5, 10, 30, 60, 120 and 180 min following injection, centrifuged in capillary tubes, and 10 pi of plasma analyzed for radioactivity. Three /A aliquots were pipetted directly into 10 ml scintillation fluid (toluene-PPO: 5 g/1) and the total counts in each sample were determined. The remaining 7 /J was added to 0.5 ml water and the material was then partitioned twice between chloroform and water. The organic phase was evaporated to dryness, redissolved in 50 M! of absolute ethanol, and chromatographed on fluorescent-indicator thin-layer tapered strips 2 X19 cm (Eastman-chromagram No. 6060) using a chloroform-methanol (97:3) solvent. Cold corticosterone was run as a marker and 0.5 cm strips were cut out and placed in 10 ml scintillation fluid and counted in a Beckman LS150 liquid scintillation counter. Trial experiments indicated that similar counts were obtained whether silica gel was scraped off the plastic backing into the vial or the whole 0.5 cm section was counted after being added directly to the counting vial. Results and Discussion In all cases the position of the radioactive peak in the thin-layer chromatogram corresponded to the position of the corticosterone marker. Therefore, counts obtained from the plasma samples were a valid indication of the corticosterone content of the plasma and were used in calculating the corticosterone half-life