Showing papers on "Corticosterone published in 1986"

Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus.

Abstract: The neonatal rat shows a period of decreased responsiveness to noxious stimuli during the first 3 weeks of life, but the nature of this impairment is still controversial. To test the functionality of the hypothalamus-pituitary-adrenal axis during this period, we studied pituitary and adrenal responsiveness to exogenous ovine CRF and the ability of various stressors (ether vapors, electroshocks, and hypoxia) to elicit ACTH and corticosterone secretion. We also measured hypothalamic CRF content and pituitary ACTH content as well as CRF-binding sites in the anterior pituitary. From days 3–10, small elevations in plasma ACTH and corticosterone levels were observed after a 3-min exposure to ether vapors or electroshocks. In contrast, during this period, a 20- min exposure to hypoxia (5% O2 in N2) was unable to trigger measurable ACTH secretion, while corticosterone was significantly elevated. From days 14–21, plasma ACTH and corticosterone levels increased significantly after exposure to ether stress, hypoxia,...

Glucocorticoid toxicity in the hippocampus. Temporal aspects of synergy with kainic acid.

Abstract: Excessive exposure to glucocorticoids can damage neurons of the hippocampus, the principal neural target tissue for the steroid. Glucocorticoids, which are broadly catabolic throughout the body, appear to damage the hippocampus by inducing a metabolic vulnerability in its neurons, impairing their capacity to survive varied neuropathologic challenges which would normally be sublethal. As such, a number of interventions which damage the hippocampus--infusion of an excitotoxin or of an antimetabolite or induction of global ischemia--have their toxicity enhanced in rats with high circulating corticosterone concentrations and attenuated in adrenalectomized animals. The present report examines the temporal parameters with which corticosterone modulates the toxicity of the excitotoxin kainic acid (KA). Rats adrenalectomized and maintained corticosterone-free for 1 week prior to and following microinfusion of KA had minimal volumes of hippocampal damage. Administration of 10 mg/day of corticosterone (which produces circulating concentrations in the upper physiological range for the majority of a day) for as little as 1 day prior to and following KA infusion significantly potentiated damage; increasing periods of exposure to corticosterone bracketing the infusion of the toxin progressively increased damage. Both exposure to corticosterone only during the period prior to KA infusion or only in the aftermath of infusion potentiated damage. Thus, glucocorticoids appear to compromise the capacity of hippocampal neurons to survive KA via both rapid effects (manifest within as little as 24 h) as well as through more persistent actions.

Plasma corticosterone responses to electrical stimulation of the amygdaloid complex: cytoarchitectural specificity.

Abstract: To pursue the possibility that subdivisions within the amygdaloid complex are differentially involved in adrenocortical function, plasma samples obtained prior to and following electrical stimulation of the amygdala of urethane (1.30 g/kg) anesthetized female rats were assessed for corticosterone concentration. Hippocampal EEG, ECG, heart rate, mean arterial pressure, and respiration routinely were monitored, and timed blood samples (0.2 ml) were obtained from a catheterized artery. Blood samples were taken 0.5 min prior to and at 5, 10, 15, and 30 min after initiation of stimulation. Whereas stimulation of the central and lateral nuclei produced a decrease (p less than 0.05) in plasma corticosterone, stimulation of the basomedial, medial and posterior corticomedial nuclei resulted in increased plasma corticosterone levels (p less than 0.05). In contrast, no change in corticosterone levels were observed following sham stimulation or stimulation of several nonamygdaloid sites. Collectively, these data support the hypothesis that subdivisions within the amygdaloid complex are differentially involved in adrenocortical function.

Aldosterone effects on salt appetite in adrenalectomized rats.

Abstract: In order to establish the in vivo specificity of the mineralocorticoid recognition system of the rat brain, we investigated the potencies of aldosterone (ALDO) and corticosterone (CORT) in suppressing

Diurnal Variation in Neuroendocrine Response to Stress in Rats: Plasma ACTH, β-Endorphin, β-LPH, Corticosterone, Prolactin and Pituitary Cyclic AMP Responses

Abstract: The effects of restraint stress applied at different times of the day on levels of five stress-responsive plasma hormones (ACTH, β-endorphin, β-LPH, corticosterone and prolactin) and pituitary cyclic AMP levels were assessed. Different groups of rats were subjected to 15 min of restraint stress at 2-hour intervals over a 24-hour period. Rats were sacrificed immediately upon removal from their home cage (controls) or immediately following restraint (stressed). The time of day of stress exposure markedly affected the stress responses measured. Generally, responses to stress applied at the beginning of the dark cycle (18.00) were less than those seen following stress applied at the beginning of the light cycle (06.00). Stress at 06.00 increased levels of pituitary cyclic AMP 10-fold, while stress applied at 18.00 did not significantly increase pituitary cyclic AMP levels. In stressed rats, high correlations were seen among levels of hormones derived from the common precursor, proopiomelanocortin (ACTH, β-endorphin, β-LPH) and between these hormones and levels of pituitary cyclic AMP. These findings support the hypothesis that pituitary cyclic AMP is involved in the stress-induced release or synthesis of the pituitary hormones ACTH, β-endorphin, and β-LPH.

Stressor controllability and the pituitary-adrenal system

Abstract: Stressor controllability can alter both behavior and pituitary-adrenal activity. Potential mediation of these behavioral effects by differential pituitary-adrenal output requires that the precise conditions that lead to differential behavioral consequences also produce differential pituitary-adrenal activity. Both plasma ACTH and corticosterone levels were measured at various times following escapable and yoked inescapable electric shock conditions known to produce differential behavioral outcomes. The escapable and inescapable shock procedures did not produce a detectable differential effect. Both shock conditions produced equivalent elevation of ACTH and corticosterone. Neither decay rates nor the ACTH and corticosterone response to shock reexposure differed among shocked groups.

Increased pituitary sensitivity to glucocorticoid feedback during the stress nonresponsive period in the neonatal rat.

Abstract: Neonatal rats show a diminished response to stress [the stress-nonresponsive period (SNRP)] from day 2–3 until day 14 of age; the physiological bases for the SNRP are unknown. We examined whether enhanced sensitivity of the brain or pituitary to the inhibitory feedback effects of circulating glucocorticoids (GC) contributes to the SNRP. Age-related changes in the ability of corticosterone (CORT) and dexamethasone (DEX) to inhibit the ACTH secretion induced by urethane or CRF were studied. We also examined the ACTH response to ether stress or CRF in intact or 24 h-adrenalectbmized 5-dayold rats. Plasma ACTH did not increase in intact rats after ether stress (basal: 64.6 ± 9.1 pg/ml vs. stressed: 66.8 ± 8.9 pg/ml; P > 0.05), whereas small elevations occurred after CRF challenge (184.6 ± 40 pg/ml; P ≤ 0.01). Five-day-old adrenalectomized rats, which had elevated basal ACTH concentrations, increased ACTH secretion after exposure to ether or CRF. Thus, negative feedback appears to mediate critically the SNRP. ...

Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback.

Abstract: Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 Mg/dl- Suppresion of irCRF secretion in response to nitroprussideinduced hypotension is observed and occurs at a plasma corticosterone level between 8–12 μg/dl. These studies provide further evidence for a strong central component of the delayed fe...

Reset of feedback in the adrenocortical system: an apparent shift in sensitivity of adrenocorticotropin to inhibition by corticosterone between morning and evening.

Abstract: There is evidence in man and rats that higher circulating levels of glucocorticoids are required to normalize basal unstimulated ACTH levels at the peak of the circadian rhythm than at the trough. To explore this phenomenon, we tested the inhibitory effect of constant levels of corticosterone on plasma ACTH in the morning (AM) and evening (PM) in young male rats implanted with fused pellets of corticosterone-cholesterol at the time of adrenalectomy (ADX+B) and studied 5 days later. There was a marked shift of the plasma corticosterone-ACTH inhibition curve to the right between AM and PM, demonstrating that the efficacy of corticosterone feedback inhibition of ACTH is less in the PM. Comparison of plasma ACTH and corticosterone levels during 24 h in sham-adrenalectomized rats (SHAM-ADX), adrenalectomized rats (ADX), and ADX+B revealed constantly low ACTH in SHAM-ADX, constantly high ACTH in ADX, and biphasic ACTH levels in ADX+B. Corticosterone levels were biphasic in SHAM-ADX and were constant in the other two groups. These results again showed a shift in corticosterone feedback efficacy as a function of the time of day and also suggested that basal ACTH secretion is maintained in the low normal range in intact rats because of the marked diurnal rhythm in corticosterone. The sensitivity of the pituitary ACTH response to exogenous CRF did not change between AM and PM in either intact or ADX+B showing that the shift in feedback sensitivity to corticosterone does not reside in the pituitary. The response of the entire adrenocortical system to histamine stress was shown to be equivalent in both the AM and PM, suggesting that feedback sensitivity of the entire system to corticosterone does not change as a function of the time of day. We conclude from these results that there is an apparent diurnal change in ACTH sensitivity to corticosterone feedback that can be defined operationally as reset. We believe that the site of feedback being tested shifts solely from the pituitary in the AM (at the nadir of the rhythm) to the brain and the pituitary in the PM (at the peak of the rhythm). The lack of the normally high transients of corticosterone that occur in SHAM-ADX rats results in increased brain drive of the pituitary in ADX+B.

Stress-induced suppression of testosterone secretion in male alligators.

Abstract: In order to test the effect of acute stress on gonadal hormone secretion in reptiles, six mature male alligators were captured, and a blood sample was taken within 5 min of capture. Additional blood samples were taken at timed intervals for up to 41 hr, and plasma testosterone and corticosterone were measured by radioimmunoassay. Plasma testosterone declined to 50% of the initial value by 4 hr and dropped to less than 10% of initial by 24 hr. Plasma corticosterone increased during the first 12 hr, declined at 24 hr, and rose again at 40 hr. Blood samples from male alligators collected in North and South Carolina, south Florida, and in south Louisiana in two consecutive breeding seasons were also assayed for testosterone and corticosterone. In these populations there were significant differences in mean plasma testosterone and corticosterone levels. Elevated corticosterone levels were consistently seen in alligators caught in traps and from which a blood sample was taken several hours later. Plasma testosterone, although consistently lower in trapped alligators, did not show a negative correlation with plasma corticosterone. Farm-reared alligators bled once, released, and bled again at 24 hr also showed a highly significant suppression of testosterone secretion. These results demonstrate that stress has a rapid and dramatic effect on testicular steroid secretion in both farm-reared and wild alligators.

Differential effects of transforming growth factor type beta on the growth and function of adrenocortical cells in vitro

Abstract: Transforming growth factor type beta (TGF-beta) suppresses basal as well as corticotropin (ACTH)-stimulated steroid formation by bovine adrenocortical cells in culture. The effect is dose dependent and is not accompanied by any change in adrenocortical cell growth. The minimum effective dose of TGF-beta is 4 X 10(-13) M (10 pg/ml), and maximal inhibition is observed at a concentration of 4 X 10(-11) M (1 ng/ml). A 16- to 20-hr incubation with TGF-beta is required to decrease steroidogenesis, and 12-18 hr are required before cells treated with TGF-beta recover complete responsiveness to corticotropin. Increases in cAMP mediated by corticotropin, forskolin, and isobutylmethylxanthine are not modified by the addition of TGF-beta; thus adenylate cyclase activity is unaffected by TGF-beta. Although TGF-beta inhibits the formation of all of the delta 4-steroids measured (including cortisol, corticosterone, aldosterone, and androstenedione), its effect can be completely reversed by the addition of 25-hydroxycholesterol, pregnenolone, or progesterone to the cells. In contrast, the addition of low density lipoprotein has no effect suggesting that TGF-beta targets the conversion of cholesterol precursors to cholesterol. The results demonstrate a highly potent effect of TGF-beta on the differentiated function of the adrenocortical cell. The inhibition of steroidogenesis can be dissociated from any effect on cell proliferation, and it occurs distal to the formation of cAMP but proximal to the formation of cholesterol. The results suggest that in the adrenal, TGF-beta or TGF-beta-like proteins may be playing an important role in modifying the differentiated state of the adrenocortical cell.

Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats.

Abstract: Metabolic defects in obese (fa/fa) Zucker rats have previously been shown to be reversed by adrenalectomy; however, hypercorticosteronemia has not been demonstrated. We now report that the total daily excretion of corticosterone and urea nitrogen are significantly greater (P less than 0.01) in obese Zucker rats than in age-matched lean Zucker rats. This excessive excretion of corticosterone is not of autonomous adrenal origin, since dexamethasone treatment (20 micrograms/kg X day) for 2 days induced a proportionate reduction in corticosterone excretion (approximately 50%) in both obese and lean Zucker rats. Corticosterone excretion was further suppressed to levels not different from those in lean rats after 2 days of dexamethasone (40 micrograms/kg X day). Both the peak and total pituitary beta-endorphin secretion in response to an iv bolus of corticotropin-releasing factor (CRF) were diminished in obese Zuckers. The response to CRF in obese Zucker rats was dampened and superimposable on that of dexamethasone-treated lean Zucker rats, suggesting the existence of chronic hypercorticosteronemia as a component of this genetic obesity. These observations provide evidence for a compensatory alteration of the pituitary-adrenal axis. We suggest that corticosterone turnover may be increased in obese Zucker rats.

Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. A coupled stereological and enzymological study.

Abstract: Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 11 beta-hydroxylase (11 beta OH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the "aldosterone-escape" phenomenon). The activities of 3 beta HSD and 11 beta OH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata cell-types. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11 beta OH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the "aldosterone-escape" phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3 beta HSD and 11 beta OH.

Biochemical and behavioral correlates of chronic stress: effects of tricyclic antidepressants.

Abstract: Using a chronic stress model of depression, the biochemical, hormonal, and neurochemical effects of chronic stress were determined in male CD-1 mice. The effects of chronic administration of three tricyclic antidepressants (TCA): chlorimipramine, amitriptyline and desmethylimipramine, as well as fluoxetine, a specific serotonin uptake inhibitor, were also evaluated. Exposure to acute noise/light stress dramatically increased motor activity (behavioral activation) in comparison with basal (unstressed) activity. However, animals with a history of chronic stress exhibited reduced basal activity levels as well as a decreased behavioral activation response to acute stress. There was also exaggerated corticosterone (CS) responding in both of these behavioral test situations attributable to prior chronic stress exposure. Chronic treatment with any of the TCAs significantly restored the behavioral activation response to acute stress and normalized CS responding in chronically stressed animals. Chronic fluoxetine treatment was ineffective. In chronically stressed, but behaviorally untested (quiescent) mice, there were no changes in CS levels, but norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased. However, chronically stressed mice tested for basal motor activity showed large NE decreases, while those receiving acute stress exposure prior to testing showed large NE decreases and further 5-HIAA increases. There were no alterations on neurochemical parameters due to any drug treatment which could be correlated with a possible mechanism for their efficacy, although evidence suggested NE involvement. It was further proposed that the chronic stress paradigm induced conditioned neuroendocrine and neurochemical responses.

Central nervous system control of hyperphagia in hypothalamic obesity: dependence on adrenal glucocorticoids.

Abstract: Gold thioglucose (GTG)-treated hyperphagic obese mice exhibit a pronounced anorexia upon adrenalectomy which is reversed by the systemic administration of adrenal glucocorticoids. To determine whether the return of hyperphagia was mediated by an action of the hormones on the central nervous system, food intake and body weight were monitored in anorexic GTG-treated obese adrenalectomized mice which received a single intracerebroventricular (icv) injection of very small amounts of adrenal glucocorticoids, including cortisone, corticosterone, and dexamethasone. The responses of untreated controls and adrenalectomized control mice were also studied. To rule out possible systemic effects of icv injections of adrenal glucocorticoids, food intake and body weight were also monitored in similar mice given a single ip injection of the hormones. We found that hyperphagia was restored and weight loss abolished in anorexic GTG-treated obese adrenalectomized mice after a single icv injection of adrenal glucocorticoids;...

Central norepinephrine and plasma corticosterone following acute and chronic stressors: Influence of social isolation and handling

Abstract: Exposure to acute inescapable shock resulted in a decline of hypothalamic norepinephrine (NE), and an increase of plasma corticosterone concentrations. With repeated application of the stressor over 15 successive days the reduction of NE was eliminated and concentrations of the amine actually exceeded those of control animals. In contrast to the NE variations, plasma corticosterone concentrations were elevated irrespective of whether mice received a single or repeated sessions of inescapable footshock. Moreover, unlike NE concentrations, handling mice on successive days in the absence of the shock treatment was sufficient to provoke a modest, but reliable increase of corticosterone concentrations. It is suggested that the hypothalamic NE and plasma corticosterone changes may be reflective of different attributes of the stressor or are subserved by different mechanisms. It is suggested that variations in both these systems represent adaptive changes to meet environmental demands.