EFFECTS OF A SPECIFIC GLUCOCORTICOID RECEPTOR ANTAGONIST ON CORTICOTROPIN-RELEASING HORMONE GENE-EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE NEONATAL RAT

Mechanisms controlling the synthesis of corticotropin releasing hormon e (CRH) in neonatal rats, and the ontogeny of glucocorticoid (GC) feed back control of hypothalamic CRH remain unknown. Specific issues are w hether stress induces up-regulation of CRH gene expression during the first postnatal week, and the role of GC feedback, at the hypothalamic level, in the stress-hyporesponsive period. We studied the ontogeny o f the negative feedback regulation of CRH gene expression by GC in the paraventricular nucleus (PVN). We implanted chronic cannulae containi ng a GC-receptor antagonist, RU 38486, in rats on postnatal days 3 to 13. Three days later, animals were sacrificed, and brains were analyze d for CRH-messenger RNA (CRH-mRNA), using semi-quantitative in situ hy bridization. Animals implanted with cholesterol-containing cannulae se rved to evaluate the stressful effect of implantation on CRH-mRNA abun dance. The presence of GC receptor messenger RNA (GR-mRNA) in the PVN of neonatal rats was also determined. RU 38486 did not increase CRH-mR NA abundance during the first postnatal week, despite the presence of GR-mRNA in the PVN. Chronic-implantation stress also failed to increas e CRH synthesis. CRH gene expression in the PVN was enhanced in infant rats implanted with RU-38486 on postnatal day 9 or later. Cholesterol implantation on days 9, 10 (but not later), resulted in increased PVN -CRH-mRNA. Thus, CRH-mRNA is up-regulated by chronic blockade of GC re ceptors only subsequent to the eighth postnatal day. Furthermore, such blockade does not affect the response of CRH-MRNA to chronic stress i n the neonatal rat.