The developmental profile of the corticotropin releasing factor receptor (CRF 2) in rat brain predicts distinct age-specific functions

Abstract

Corticotropin releasing factor (CRF) activates two known receptor types, CRF 1 and CRF 2. In the adult rat brain, CRF 2 has a distinct distribution pattern, suggesting that it may mediate functions exclusive of CRF 1. The goal of this study was to determine the age-dependent distribution of CRF 2-messenger RNA (CRF 2-mRNA) in the rat brain. Brains from rats sacrificed under stress-free conditions on fetal days (F) 15, 16, 17 and 19, and postnatal days 1, 3, 5, 7, 9, 12, 15, 25, 49 and 90 (adult) were analyzed using semiquantitative in situ hybridization histochemistry. The onset and distribution of CRF 2-mRNA in the developing rat brain revealed important differences from the adult expression pattern: earliest expression of CRF 2-mRNA was observed in the ventromedial hypothalamus (VMH) on F16. High levels of CRF 2-mRNA were present in the fronto-parietal cortex in the fetal and early postnatal brain but not later. Conversely, no CRF 2-mRNA was detectable in the ventroposterior (lateral and medial) thalamic nuclei prior to postnatal day 7. Distinct developmental profiles of CRF 2-mRNA were also observed in the lateral septum, medial, basal and cortical amygdala nuclei, and in several hippocampal fields. In conclusion, CRF 2 is expressed in the hypothalamus on F16, prior to the detection of CRF itself in the paraventricular nucleus. The differential levels and distributions of CRF 2-mRNA in hypothalamic and limbic brain regions indicate a precise regulation of this receptor's expression during development, as shown for CRF 1. Regulation of the levels of CRF 2 may modulate the effects of CRF (and related ligands) on target neurons, consistent with differential maturation of the functions mediated by this receptor.