Neonatal facilitation of stress-induced adrenocorticotropin secretion by prior stress: evidence for increased central drive to the pituitary.

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Abstract
The adrenocortical system of the neonatal rat exhibits both normal pituitary (ACTH) and blunted adrenal corticosterone (B) responses to a variety of different stressors. It is established that although circulating levels of B are low during the first 2 weeks of life, efficient inhibition of ACTH secretion by B is observed in neonatal rats. We investigated the ability of the hypothalamo-pituitary unit to respond to two consecutive, 1 h apart, exposures to 3 min ether vapor (stress 1 and stress 2) and whether an exogenously provided B signal that mimicked the amount of B secreted after the first stress could impair stress-induced ACTH secretion. We also determined in vivo and in vitro whether previous stress could alter pituitary responses to CRF, arginine vasopressin (AVP), or a combination of both peptides. After stress 2, 10-day-old neonates showed similar or increased peak (5 min = control) ACTH secretion compared to stress 1, although the area under the curve over 60 min after stress was comparable between stresses 1 and 2. Stress-induced B secretion was significantly elevated (P < 0.05) 60 min after stress 1, and the mean area (n = 5 experiments) was 39.3 +/- 14 micrograms/dl.60 min. Exogenously injected B (0.1 mg/kg BW) instead of stress 1 was able to mimic the magnitude of the B signal observed after stress 1 (area = 56.4 micrograms/dl.60 min) and significantly reduced (56.4 +/- 18% of ether peak) the peak ACTH secretion seen after stress 2. Doses of 1 and 0.01 mg B/kg BW also reduced peak ACTH amplitude to 20.6 +/- 6.6% and 73.7 +/- 30% of the ether peak value, respectively. Previous exposure to ether stress did not affect the in vivo ACTH response to CRF (10 micrograms/kg) or AVP (5 micrograms/kg) measured 30 min after ip injection, but increased (P < 0.05) the response to CRF plus AVP treatment. When pituitaries from previously stressed 13-day-old pups were incubated in vitro, basal ACTH release was increased, and the ACTH response to CRF (1 and 10 nM), expressed as a percentage of the control value, was reduced. A similar observation was made when intact pituitaries were treated with CRF (0.1 nM) during the preincubation period.(ABSTRACT TRUNCATED AT 400 WORDS)

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