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 hormone (CRH) in neonatal rats, and the ontogeny of glucocorticoid (GC) feedback control of hypothalamic CRH remain unknown. Specific issues are whether 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 of the negative feedback regulation of CRH gene expression by GC in the paraventricular nucleus (PVN). We implanted chronic cannulae containing a GC-receptor antagonist, RU 38486, in rats on postnatal days 3 to 13. Three days later, animals were sacrificed, and brains were analyzed for CRH-messenger RNA (CRH-mRNA), using semi-quantitative in situ hybridization. Animals implanted with cholesterol-containing cannulae served to evaluate the stressful effect of implantation on CRH-mRNA abundance. The presence of GC receptor messenger RNA (GR-mRNA) in the PVN of neonatal rats was also determined. RU 38486 did not increase CRH-mRNA abundance during the first postnatal week, despite the presence of GR-mRNA in the PVN. Chronic-implantation stress also failed to increase 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 receptors only subsequent to the eighth postnatal day. Furthermore, such blockade does not affect the response of CRH-mRNA to chronic stress in the neonatal rat.
Yi
S J
SJ
Department of Neurology, University of Southern California, Los Angeles 90027.
Masters
J N
JN
Baram
T Z
TZ
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000008:administration & dosage / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D003348:Cortisone / Q000097:blood; D015342:DNA Probes; D004343:Drug Implants; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D013312:Stress, Physiological / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D015342:DNA Probes; D004343:Drug Implants; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003346:Corticotropin-Releasing Hormone; D002784:Cholesterol; D003348:Cortisone