title: The pituitary-adrenocortical system of neonatal rats is responsive to stress throughout development in a time-dependent and stressor-specific fashion.
abstract: The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life. Although we previously found full responsiveness of the hypothalamus-pituitary unit to adrenalectomy in young rats [days (d) 5-10], we failed to measure a significant increase in ACTH 10 min after ether administration until d14 of age. These studies were, therefore, designed to test the functional activation of the HPA axis after a single or repeated exposures to stress. Both qualitative (time-course, stressor-specific, circadian) and quantitative changes in the ACTH and corticosterone (B) responses to various stressors were tested during the first 10 days of life. Exposure to 3 min of ether vapor increased ACTH and B secretion (P less than 0.05-0.01) in 1-, 5-, and 10-d-old rats, with an increasing amplitude of both ACTH and B responses as a function of age. Peak secretion of ACTH occurred 5 min after the onset of stress (122 +/- 3.8 to 359 +/- 54 pg/ml on d1-10), while the time of maximal B increased as a function of age. Other stressors, such as maternal separation (12 h), cold (4 C; 60 min), or histamine injection (4 mg/kg BW, ip), provoked significant and stressor-specific ACTH and B responses in 10-d old rats. Histamine administration increased ACTH secretion above that of vehicle-injected rats, with a peak of secretion 15 min after drug injection (272 +/- 29 vs. 127 +/- 8 pg/ml; P less than 0.01). Histamine-induced B secretion peaked at 60 min (3.7 +/- 0.5 micrograms/dl). In contrast to early responses observed after ether, separation, or histamine stress, cold stress in 10-d-old pups caused a large ACTH and B release 4 h after the onset of cold compared to that in maternally deprived pups [ACTH: cold, 457 +/- 61 pg/ml; separated, 150 +/- 14 (P less than 0.01); B: cold, 3.3 +/- 0.4 micrograms/dl; separated, 1.8 +/- 0.2 (P less than 0.05)]. We did not detect morning-evening (AM-PM) differences in either the pattern or the magnitude of the ACTH or B response to maternal separation or cold stress. Suppression of cold-induced ACTH release by B injection (1 mg/kg BW) 2 h before stress was observed until 4 h after stress in the AM and PM, whereas when given after cold, B was less effective in the PM than in the AM at preventing the rise in ACTH levels observed at 4 h.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, University of California, San Francisco 94143-0444.
authors.forename: C D
authors.initials: CD
authors.lastname: Walker
authors.forename: K A
authors.initials: KA
authors.lastname: Scribner
authors.forename: C S
authors.initials: CS
authors.lastname: Cascio
authors.forename: M F
authors.initials: MF
authors.lastname: Dallman
mesh_terms: D000302:Adrenal Cortex / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000378:metabolism; D003080:Cold Temperature; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006632:Histamine; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001127:Arginine Vasopressin; D006632:Histamine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone