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The possible existence of periods of sensitivity to elevated levels of corticosterone in the postnatal development of the pituitary-adrenal axis was investigated. Long-Evans rats were implanted ip with corticosterone (25 mg/100 g body wt) mixed with an equal amount of cholesterol on postnatal days 3, 6, 12 or 18. Eight blood samples were obtained from each animal at various ages by cardiac puncture. Steroid treatment during the first postnatal week resulted in lowered adult basal levels of plasma corticosterone without affecting the diurnal rhythm. Males treated on day 3 had lowered peak (PM) and trough (AM) levels of the steroid as adults, while males treated on day 6 showed only a lowered PM level. A similar reduction in basal levels of plasma corticosterone was observed in immature females, but did not persist into adulthood. Steroid treatment at day 12 had no effect on basal or diurnal pituitary-adrenal activity. Treatment at day 18 reduced the amplitude of the adult diurnal rhythm in both sexes and delayed the onset of the rhythm in males. No differences in stress responsiveness or adrenal weights were detected. Thus, two distinct periods exist in the postnatal development of the rat during which basal and diurnal pituitary-adrenal activity can be differentially and persistently altered by treatment with the naturally occurring glucocorticoid.

Acute ethanol exposure produces activation of the brain-pituitary-adrenal (BPA) axis, resulting in the release of ACTH, beta-endorphin, and glucocorticoids. While elevated levels of plasma glucocorticoids are also found after chronic ethanol administration, plasma ACTH and beta-endorphin are normal or reduced. It is also unclear whether chronic ethanol exposure results in tolerance to the stimulatory effect of ethanol on BPA activity. To determine the site and mechanism of ethanol action on the BPA axis we studied the CRF secretory profile in a superfused rat hypothalamic preparation after chronic ethanol administration in vivo and the CRF responses after acute ethanol exposure in vitro. Superfused hypothalami from normal and pair-fed control rats released CRF-like immunoreactive material (CRF-LI) in a pulsatile manner, with a mean (+/- SE) frequency of 5.1 +/- 0.7 pulses/h. In contrast, the pulse frequency of CRF-LI release from hypothalami of rats receiving chronic ethanol treatment (fed an alcohol-containing liquid diet for 2 weeks) increased dramatically; the basal mean CRF level, pulse amplitude, and pulse duration remained unchanged. Hypothalamic CRF content was decreased. This chronic ethanol exposure also altered the dose-response characteristics of CRF release when ethanol was introduced acutely, as a pulse, into the in vitro preparation. Acute exposure to 20 mg/100 ml ethanol produced greater release of CRF-LI from control hypothalami than from chronic ethanol-exposed hypothalami. A further elevation above basal levels was produced by 200 mg/100 ml ethanol in control, but not ethanol-exposed, hypothalami. Secretion of CRF from ethanol-exposed hypothalami in response to depolarizing concentrations of potassium chloride was suppressed. Chronic ethanol treatment had no effect on CRF-LI and CRF bioactivity responses to stimulation with acetylcholine. These findings suggest the presence of a high frequency pulse-generating mechanism for CRF release in the hypothalamus. This pulsatile secretory mechanism is altered by chronic ethanol exposure of the animals in vivo. Chronic intoxication resulted in tolerance to the stimulatory effect of ethanol on CRF release in vitro.

Brain stem lesions were made by high frequency coagulation in cats that had been maintained on regular or low sodium diets. Four hours after placing the lesion, adrenal venous blood was collected for determination of the secretion rates of aldosterone and cortisol. Discrete lesions placed in the dorsal central region of the rostral midbrain, involving primarily the posterior commissure, the periaqueductal gray substance and structures immediately adjacent to it, resulted in significant reductions in aldosterone output both types of animals. Cortisol output was somewhat depressed in cats on the regular diet following discrete lesions of the rostral midbrain, while in the low sodium group the output of this steroid was unaffected. Larger lesions which involved the habenulae, the stria medullaris and/or the pineal gland, in addition to the central rostral midbrain, modified or obscured the effects of the discrete rostral midbrain lesions on steroid secretion. In animals on either diet these larger lesions re...