Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats.
Rat pups 2-14 days of age were exposed daily to handling (15 min of separation from mother and home cage), maternal separation (MS; 180 min of comparable separation), or were left entirely undisturbed (non-handled; NH). As adults, MS rats showed increased hypothalamic corticotropin-releasing factor (CRF) mRNA levels compared with NH rats, while CRF mRNA levels in H rats were significantly lower than either MS or NH animals. Hypothalamic CRF content under basal conditions followed exactly the same pattern. A 20-min period of restraint stress produced significant CRF depletion in all groups, although the percentage of depletion was significantly lower in H animals compared with either MS or NH animals. Restraint stress produced significantly higher increases in plasma corticosterone in MS and NH animals than in H animals. These data reflect the importance of early environmental factors in regulating the development of the hypothalamic CRF system and the responsiveness of the hypothalamic-pituitary-adrenal axis to stress.
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA.
P M
PM
Plotsky
M J
MJ
Meaney
D000199:Actins / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006234:Handling, Psychological; D007031:Hypothalamus / Q000254:growth & development / Q000502:physiology*; D008425:Maternal Behavior; D008473:Median Eminence / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D012149:Restraint, Physical; D012934:Social Isolation; D013315:Stress, Psychological / Q000503:physiopathology*
D000199:Actins; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone