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Differential Expression of c-fos and Tyrosine Hydroxylase mRNA in the Adrenal Gland of the Infant Rat: Evidence for an Adrenal Hyporesponsive Period

Department of Biological Sciences (D.K.O., M.S.), University of Delaware, Newark, Delaware 19716; Division of Medical Pharmacology (M.S.), Leiden/Amsterdam Center for Drug Research (LACDR), University of Leiden, 2300 RA Leiden, The Netherlands; Department of Psychology (M.K.G.), University of Delaware, Newark, Delaware 19716; CNS Diseases (G.W.D.), Bristol-Myers Squibb Pharma Company, Glenolden, Pennsylvnia 19036; and Center for Neuroscience (S.L.), University of California, Davis, California 95616

Address all correspondence and requests for reprints to: Seymour Levine, Center for Neuroscience, University of California, 1544 Newton Court, Davis, California 95616. E-mail: . slevine{at}ucdavis.edu

Rats exhibit a stress hyporesponsive period from postnatal day (PND) 4–14 in which the neonate displays a minimal corticosterone response to stress. We used the maternal deprivation model to test whether this adrenocortical hyporesponsiveness to stress results from a decrease in adrenal sensitivity to ACTH. Neonates (PND 6, 9, and 12) were injected ip with dexamethasone to block endogenous ACTH release, and 4 h later injected with graded doses of ACTH and killed. In another experiment, neonates were injected with isotonic saline and adrenal glands were collected at 30, 60, and 120 min post injection to examine c-fos and tyrosine hydroxylase mRNA levels using in situ hybridization. Maternally deprived pups demonstrated elevated corticosterone levels at the two highest ACTH doses and showed a greater magnitude in glucocorticoid secretion compared with the nondeprived pups. Maternally deprived pups given a saline injection exhibited elevated basal and stress-induced levels of corticosterone, in contrast to the nondeprived pups that showed a minimal response. Strikingly, maternally deprived pups exhibited elevated levels of adrenocortical c-fos mRNA, whereas the nondeprived pups did not. In contrast, the pattern of c-fos gene expression in the adrenal medulla in both groups did not display any correlation with glucocorticoid secretion. Tyrosine hydroxylase gene expression in the adrenal medulla was observed in both nondeprived and maternally deprived pups, with the latter exhibiting an earlier response of greater magnitude. These results demonstrate that the suppression of steroidogenesis occurs directly in the adrenal cortex and provide further evidence for an adrenal hyporesponsive period in the rat.

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