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Rapid Induction of Corticotropin-Releasing Hormone Gene Transcription in the Paraventricular Nucleus of the Developing Rat¹

Department of Biology, University of Delaware (G.W.D., S.L.), Newark, Delaware 19716-2577; and DuPont Pharmaceutical Co., Experimental Station (G.W.D., M.A.S.), Wilmington, Delaware 19880

Address all correspondence and requests for reprints to: Seymour Levine, Ph.D., Department of Psychology, University of Delaware, Newark, Delaware 19716-2577. E-mail: glevine{at}udel.edu

Neonates from postnatal days (pnd) 4–14 display a minimal pituitary-adrenal response to mild stress, the so-called stress hyporesponsive period (SHRP). However, during the SHRP, maternal deprivation (deprived) alters the pituitary-adrenal system, enabling neonates to become endocrine responsive to specific stimuli. Although neonates do display stress-induced ACTH, there is limited evidence for enhanced CRH gene expression early in development. The present experiment examined whether a mild stimulus (isotonic saline injection) administered to deprived and nondeprived neonates would enhance CRH biosynthesis in the paraventricular nucleus. Using in situ hybridization we measured the time course of CRH heteronuclear RNA (hnRNA) and messenger RNA at 15, 30, and 240 min poststimulus. Pnd 6, 12, and 18 were included to examine the CRH gene response during and outside of the SHRP. Despite the minimal endocrine response of nondeprived pups during the SHRP, CRH hnRNA and messenger RNA were elevated at 15 min (all ages). Both transcripts were enhanced at 15–30 min in deprived (pnd 12 and 18) pups; however, the magnitude of the response was less than that in nondeprived pups. These data indicate that during ontogeny there is a rapid stimulus-induced CRH biosynthesis. Thus, during development, the central components of the hypothalamic-pituitary-adrenal axis may be stress hyperresponsive rather than hyporesponsive.

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