CORTICOTROPIN-RELEASING FACTOR MESSENGER-RNA AND PEPTIDE LEVELS ARE DIFFERENTIALLY REGULATED IN THE DEVELOPING OVINE BRAIN

The regulation of CRF mRNA and protein in the developing ovine brain h as been studied to assess the hypothesis that CRF is differentially re gulated in the hypothalamus (Hypo), hippocampal-amygdala complex (H&A) , frontal cerebral cortex (FCC) and brainstem (BS). We used a quantita tive RNase protection assay and radioimmunoassay to determine mRNA and peptide concentrations. respectively, from the last third of gestatio n until term (i.e., from 95 to 142 days gestation (dg); term similar t o 145 days). The major findings from this study are: (1) Hypothalamic CRF mRNA was increased by 2-fold in 140-142 dg fetuses compared to 128 -138 and 95-123 dg fetuses; P = 0.016. (2) In the hypothalamus of 140- 142 dg fetuses, there was a 2.5-fold increase in CRF mRNA derived from polyadenylation at poly(A) sites 2, 3 or 3; P = 0.005. (3) In 128-138 dg fetuses, CRF mRNA in the frontal cortex was 2-fold higher than in the other brain regions during this time period; P=0.008. (4) CRF pept ide concentrations in the Hypo were 2.5-fold higher in 140-142 dg fetu ses compared to 95-106 and 128-138 dg fetuses; P = 0.007. (5) CRF pept ide concentrations in the frontal cortex were 5.5-fold higher in 140-1 42 dg fetuses compared to fetuses at 95-106 dg; P = 0.004. (6) CRF pep tide concentrations in the H&A were 5-fold higher in 140-142 dg fetuse s compared to 95-106 dg fetuses; P = 0.029. The results from the prese nt study demonstrate for the first time that CRF mRNA and peptide are differentially regulated in a region-specific manner during developmen t.