Increased activity of the hypothalamic-pituitary-adrenal axis of rats exposed to alcohol in utero: role of altered pituitary and hypothalamic function.
Prenatal exposure to ethanol (E) enhances the offspring's ACTH and corticosterone responses to stressors. Here, we determined the role of increased pituitary responsiveness and/or PVN neuronal activity in this phenomenon. Pregnant rats were exposed to E vapors during days 7-18 of gestation, and we compared the responses of their 55- to 60-day-old offspring (E rats) to those of control (C) dams. PVN mRNA levels of the immediate early genes (IEGs) c-fos and NGFI-B, which were low under basal conditions in all groups, showed a peak response 15 min after shocks and 45 min after LPS treatment. These responses were significantly enhanced in E, compared to C offspring of both genders. CRF, but not VP hnRNA levels were also significantly higher in the PVN of shocked E offspring. Resting median eminence content of CRF and VP, and pituitary responsiveness to CRF, were unchanged, while responsiveness to VP was marginally increased in females. These results indicate that prenatal alcohol selectively augments the neuronal activity of hypothalamic CRF perikarya.
Lee
S
S
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037, USA.
Schmidt
D
D
Tilders
F
F
Rivier
C
C
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D004597:Electroshock; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008473:Median Eminence / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012332:RNA, Heterogeneous Nuclear / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014667:Vasopressins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology
D002492:Central Nervous System Depressants; D016760:Proto-Oncogene Proteins c-fos; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D014667:Vasopressins; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D020932:Nerve Growth Factor; D003345:Corticosterone