RU-486 blocks stress-induced enhancement of proenkephalin gene expression in the paraventricular nucleus of rat hypothalamus.
The purpose of this study was to investigate the glucocorticoid (GC) mediated regulation of corticotropin-releasing hormone (CRH) and proenkephalin (PE) gene expressions in the paraventricular nucleus (PVN) of the hypothalamus during physical stress induced by a single intraperitoneal (i.p.) injection of hypertonic saline (9% NaCl). Previous intracerebroventricular (i.c.v.) administration of the type II glucocorticoid receptor (GR) antagonist RU-486 (20 ng/rat), increased the basal CRH mRNA levels in the PVN but had no effect on PE gene expression. Stress induced by injection of hypertonic saline increased both CRH and PE mRNA levels in PVN. Administration of RU-486 completely blocked the stress-induced increase of PE mRNA levels, but failed to alter the CRH mRNA levels in the PNV. These data suggests that, under these experimental conditions, endogenous GC are necessary for a normal PE response to hypertonic saline stress.
García-García
L
L
Departamento de Farmacologia, Facultad de Farmacia and Instituto Pluridisciplinar Universidad Complutense, Madrid 28040, Spain.
Harbuz
M S
MS
Manzanares
J
J
Lightman
S L
SL
Fuentes
J A
JA
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000235:genetics*
D004745:Enkephalins; D006727:Hormone Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D015735:Mifepristone; D003346:Corticotropin-Releasing Hormone