Showing papers on "Corticosterone published in 1984"

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response

Abstract: The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.

Stress Down-Regulates Corticosterone Receptors in a Site-Specific Manner in the Brain*

Abstract: We have examined whether corticosterone receptor number within the brain can be regulated by its own ligand and whether such autoregulation reduces receptor number after the sustained secretion of corticosterone during repeated stress. Glucocorticoid receptors were measured in cytosolic preparations from acutely adrenalectomized rats using [1,2,6,7-3H] dexamethasone; maximal binding and receptor affinity parameters were determined by Scatchard analysis. Sustained elevations of circulating corticosterone, whether by repeated stress or exogenous corticosterone administration, did not change receptor affinity for [3H] dexamethasone, but significantly reduced cytosolic corticosterone receptor number. This reduction in total receptor number could not be attributed to residual tissue contamination with endogenous corticosterone after adrenalectomy or to translocation of cystosolic receptors to cell nuclei. The receptor reductions were anatomically specific, occurring in the hippocampus and amygdala, but not in ...

Differential Effects of Maternal Stress on Circulating Levels of Corticosterone, Progesterone, and Testosterone in Male and Female Rat Fetuses and Their Mothers*

Abstract: Testosterone, progesterone, and corticosterone titers were measured by RIA in plasma of stressed and control pregnant rats and their male and female fetuses on days 17, 18, 19, and 21 of gestation and on the day of birth. The regimen of stress used (three 45-min periods of restraint under intense illumination daily from days 14–21 of pregnancy) causes failure of masculinization and defeminization of behavioral potentials in male offspring. In fetuses of both sexes, corticosterone titers increased sharply between days 17 and 18 postconception (pc) to a peak that was maintained through day 19 and then declined. This pattern resembled that obtained for testosterone in control male fetuses in which the levels of testosterone also rose sharply between days 17 and 18 pc. Corticosterone titers were elevated in samples obtained during the middle of the stress session from both the mothers (serum) and their male and female fetuses (plasma). Increased corticosterone levels were no longer evident in samples obtained...

Stress and adrenal function.

Abstract: The natural environment is composed of various potentially hostile stressors. It is a basic requirement of life that the cells of an organism must be maintained within closely defined physiological limits. The maintenance of a constant interior mileu results from physiological and behavioural homeostatic adaptations. The physiological regulation of homeostatis is achieved by complex endocrine interactions, principally by the hormones secreted from the adrenal glands. In this brief review the responses of the avian adrenal glands to stressful stimuli, the mechanism of adrenal activation, and the function of the adrenal responses will be considered.

Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF).

Abstract: The acute i.p. administration of alcohol (EtOH) to freely moving, nonanesthetized rats caused dose-related elevations in plasma adrenocorticotropin (ACTH) and corticosterone levels. In vivo, injection of anticorticotropin-releasing factor (CRF) serum (i.v.) totally abolished this stimulatory effect, suggesting that the induction of CRF secretion by EtOH represents an essential modulator of its ability to release ACTH. Exposure to high levels of alcohol vapors for 7 days was accompanied by a decrease in hypothalamic CRF content. The acute exposure of cultured pituitary cells to 0.2% EtOH did not modify basal or CRF-induced ACTH release, whereas pretreatment of the cells with EtOH for 24 hr resulted in a marked decrease in both spontaneous and stimulated ACTH secretion. It is therefore possible that the long-term exposure to alcohol may result in an increase of CRF release by the median eminence, as well as in some loss of pituitary responsiveness. From these data, we hypothesize that the acute EtOH-induced activation of the hypothalamic-pituitary-adrenal axis probably takes place at the level of CRF-secreting neurons and that this effect may play a role in the disturbance of ACTH and corticosteroid secretion observed during chronic exposure to alcohol.

Differences in Hypothalamo-Pituitary-Adrenocortical Activity in the Rat after Acute and Prolonged Treatment with Morphine

Abstract: The influence of opioid substances on the secretion in vivo and in vitro of corticosterone, corticotrophin (ACTH) and corticotrophin releasing factor (CRF) in the rat was studied. Rats given a single

Elevated corticosterone levels. A possible cause of reduced axon sprouting in aged animals.

Abstract: Measurements of serum corticosterone taken at three times in the diurnal cycle (08.00, 18.00, and 23.30 h) showed that aged male Sprague-Dawley rats have higher nonstressed circulating levels at two time points measured. To determine if such elevated levels of steroids were sufficient to interfere with lesion-induced sprouting, the corticosterone peak at 18.00 h of either aged or young adult animals was maintained in young adrenalectomized rats by use of subcutaneous corticosterone pellets. The normal young adult animal levels resulted in mild suppression of the adrenergic sprouting response seen in hippocampus following transection of the fimbria-fornix. Young animals maintained at the elevated corticosterone levels of normal senescent rats had marked suppression of sprouting. The levels of circulating glucocorticoids reached by aged rats are sufficient to retard sprouting, and may therefore interfere with synaptic turnover and the response of the senescent brain to damage.

Differential plasma corticosterone responses to hippocampal stimulation.

Abstract: The effect of limbic forebrain stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of urethane (1.20 g/kg) anesthetized female rats. Cortical electroencephalogram (EEG), electrocardiogram (ECG), heart rate (HR), mean arterial blood pressure (MAP), and respiration were routinely monitored. Timed blood samples (0.25 ml) were obtained from a catheterized femoral artery. The HR (Bts/min), MAP (mm of Hg), and corticosterone levels (microgram/dl) for 7 non-stimulated rats averaged over 6 sampling periods were 385 +/- 19,95 +/- 6, and 70.3 +/- 5.8 respectively. In electrically or sham stimulated rats, blood samples were taken just prior to stimulation (biphasic square waves, 100 microA, 50 or 60 Hz, 1 ms, 1 s on/1 s off for 15 or 30 min) and 5, 10, 15, and 30 min after initiation of stimulation. Significant changes in plasma corticosterone levels were obtained following stimulation of hippocampal and amygdaloid areas. In contrast, no change in corticosterone concentration was observed following stimulation of cortex, corpus callosum, fornix and a variety of other CNS areas. Detailed analysis of hippocampal influence on urethane stimulated plasma corticosterone levels showed increased plasma corticosterone levels following stimulation of CA1. In contrast, stimulation of CA3, dentate (includes CA4) and the subiculum produced significant decreases in plasma corticosterone levels. No change in corticosterone levels was observed following sham stimulation. Collectively, these data indicate that consideration must be given to the possibility that differential neuroendocrine regulatory mechanisms reside within various limbic forebrain complexes and that electrical stimulation of limbic forebrain sites of urethane anesthetized rats may provide information regarding sites inhibitory to pituitary-adrenal activity.

Corticotrophin releasing factor: responses in normal subjects and patients with disorders of the hypothalamus and pituitary

Abstract: Synthetic CRF-41 has been given to 43 patients with hypothalamic, pituitary or adrenal diseases and contrasted with the responses in 20 normal subjects. In the normal subjects the mean increment in serum cortisol (+/- SE) was 276 +/- 38 nmol/l; the increments showed a significant negative correlation with the basal serum cortisol levels (r = -0.56; P less than 0.02). The mean peak serum cortisol was 662 +/- 34 nmol/l and the mean peak corticosterone was 28.6 +/- 3.8 nmol/l. There was a significant positive correlation between the peak serum corticosterone and cortisol concentrations (r = 0.84; P less than 0.0001). Dexamethasone pretreatment abolished the rise in cortisol in response to CRF-41. The peak serum cortisol following CRF-41 was not significantly different between the normal subjects and those patients with pituitary disease who had normal cortisol responses to insulin-induced hypoglycaemia. However, in individual patients the peak cortisol levels induced by hypoglycaemia were greater than, but significantly correlated with, those induced by 100 micrograms of CRF-41. Seven patients were ACTH deficient in response to hypoglycaemia, and of these six responded normally to CRF-41. Only one of these patients had a lesion clearly originating in the hypothalamus; four had pituitary tumours with suprasellar extensions and the remaining patient had idiopathic GH and ACTH deficiency. Our data suggest that these patients have a functional defect of ACTH secretion due to the failure of CRF to reach the corticotroph. Of the four patients with pituitary-dependent Cushing's disease who were on no treatment at the time of testing, three showed an exaggerated and one a normal response to CRF-41. These normal or enhanced responses of hypercortisolaemic patients with Cushing's syndrome contrast with the complete inhibition of the responses to CRF-41 in normal subjects given dexamethasone. In the treated patients with Cushing's syndrome and normal serum cortisol levels, those with pituitary-dependent disease showed an enhanced ACTH response to CRF-41 as compared with the ectopic ACTH group, but there was some overlap between the two groups. Acromegalic patients did not show a GH response to CRF-41. We conclude that administration of CRF-41 is a safe new method for investigating disorders of the hypothalamo-pituitary axis.

Etomidate suppresses adrenocortical function by inhibition of 11 beta-hydroxylation.

Abstract: We studied the effect of short term infusion of the imidazole-derived anesthetic agent etomidate on plasma concentrations of ACTH, cortisol, and the cortisol-precursors 11-desoxycortisol and 17-hydroxyprogesterone. During the infusion of etomidate, a significant increase in the peripheral concentration of ACTH occurred, while plasma cortisol concentrations decreased. After the end of the infusion, cortisol concentrations further decreased, while the concentrations of desoxycortisol and 17-hydroxyprogesterone increased. Furthermore, in in vitro experiments with isolated rat pituitary and adrenal cells, etomidate did not affect corticotropin-releasing hormone-induced ACTH secretion from pituitary cells, whereas ACTH-stimulated corticosterone secretion from adrenal cells was inhibited by addition of etomidate in concentrations which occur in plasma during and after infusion of the drug. These results lead to the conclusion that etomidate inhibits adrenal 11 beta-hydroxylation.

The Natural History of Salt-Wasting Disorders of Adrenal and Renal Origin*

Abstract: Twenty one patients with selective aldosterone deficiency due to type 2 corticosterone methyl-oxidase defect [hypoaldosteronism (HA)] and 7 with pseudohypoaldosteronism (PHA) were studied longitudinally for up to 18 yr. All individuals had spontaneous and progressive normalization of sodium and fluid balance with age. The severity of the clinical manifestations varied from acute salt-wasting crisis in infancy and unexplained short stature in childhood to an asymptomatic state in adults detectable only by biochemical studies. Infants with HA had extremely elevated plasma renin activity (PRA; 70–650 ng angiotensin I/ml: h), which gradually decreased with age, and PRA was normal in adults. Cortisol followed a similar pattern, but marked elevations of plasma deoxycorticosterone (DOC; 28-553 ng/dl) and 18-hydroxycorticosterone (18-OHB; 650-6500 ng/dl) relative to aldosterone (3–29 ng/dl) persisted throughout life in all untreated patients. The plasma 18-OHB/aldosterone ratio, normally 6.2 ± 3.5 (SD), ...

Effects of corticosterone and dietary changes in the hen on ovarian function, plasma LH and steroids and the response to exogenous LH-RH.

Abstract: Ovarian regression was induced in hens by infusing 30 micrograms corticosterone/h, feeding diets deficient in Ca2+ or Na+ and by withdrawal of food and water. The weight of the ovary was most severely reduced by the corticosterone infusion. The total number of normal ovarian follicles weighing greater than 0.012 g was not altered by any of the treatments. However, the number of large yolk-filled follicles decreased while the numbers of smaller follicles and atretic follicles increased when ovarian regression was induced by dietary changes or hormone infusion as compared to normally fed or solvent-infused hens. These experimental treatments resulted in decreases in plasma concentrations of LH, progesterone and oestradiol, and increases in the plasma levels of corticosterone. These changes were immediate except for the low sodium diet with which there was a delay of about 6 days. When fasted birds were fed oats and given water, plasma LH and oestradiol, but not progesterone, increased. The infusion of corticosterone did not affect the ability of the pituitary gland to secrete LH after an injection of LH-RH, but this response was reduced or eliminated by the other experimental treatments. It is concluded that the regression of the ovary induced by these experimental treatments is a consequence of the reduction in the secretion of LH, which may itself be caused by increased plasma levels of corticosterone. It also appears that recruitment of follicles in the maturational stage which precedes entry into the hierarchy of large yolky follicles was unaffected by all of the methods of inducing ovarian regression which were studied.

Intraadrenal steroid concentrations in man: zonal differences and developmental changes.

Abstract: Adrenal gland samples from 34 individuals 0-68 yr of age were dissected into four layers of equal thickness parallel to the capsule and the zonal boundaries of the cortex, and were analyzed by RIA for their concentrations of 17OHprogesterone, 11-desoxycortisol, cortisol, progesterone, corticosterone, aldosterone, 17OH-pregnenolone, dehydroepiandrosterone, androstenedione, and testosterone, with DNA content to correct for variations in sample size. Intraadrenal steroid concentrations were 10-1000 times higher than reported serum levels, and varied significantly with age, adrenal weight, and cortical thickness. The concentrations of cortisol,11-desoxycortisol, corticosterone, androstenedione, and testosterone increased with age. Levels of 17OH-pregnenolone, dehydroepiandrosterone, and 17OH-progesterone decreased during infancy in parallel with involution of the adrenal, and then rose again in late childhood and puberty. The concentrations of all steroids, except aldosterone, increased significantly...

Endogenous blood levels of corticosterone control the immunologic cell mass and B cell activity in mice.

Abstract: An inverse relation between endogenous levels of glucocorticoids and splenic mass and cellularity was detected. Decreased endogenous corticosterone blood levels result in an increased number of immunoglobulin-secreting cells in the spleen, a fact that cannot be attributed only to the expansion of the lymphoid cell mass. The opposite phenomenon was observed in animals with high corticosterone blood levels, which showed reduced numbers of immunoglobulin-secreting cells. It is concluded that endogenous glucocorticoid levels contribute to the control of B cell activity and possibly to the interaction of these cells with other immunologic cells.

Avian endocrine responses to environmental pollutants.

Abstract: Many environmental contaminants are hazardous to populations of wild birds. Chlorinated hydrocarbon pesticides and industrial pollutants are thought to be responsible for population declines of several species of predatory birds through eggshell thinning. Studies have demonstrated that these contaminants have estrogenic potency and may affect the functioning of the gonadal and thyroidal endocrine subsystems. Petroleum crude oil exerts toxicity externally, by oiling of plumage, and internally, by way of ingestion of oil while feeding or preening. Extensive ultrastructural damage to the inner zone of the adrenal, diminished adrenal responsiveness to adrenocorticotrophic hormone, and reduced corticosterone secretion rate suggest that low levels of plasma corticosterone reflect a direct effect of petroleum on the adrenal gland. Suppressive effects of oil on the ovary and decreases in circulating prolactin have been associated with impaired reproductive function. Large-scale field studies of free-living seabirds have confirmed some of the inhibitory effects of oil on reproduction that have been observed in laboratory studies. Organophosphorus insecticides, representing the most widely used class of pesticides in North America, have been shown to impair reproductive function, possibly by altering secretion of luteinizing hormone and progesterone. Relevant areas of future research on the effects of contaminants on avian endocrine function are discussed.

Effects of pinealectomy and aging on the serum corticosterone circadian rhythm in rats.

Abstract: Male Sprague-Dawley rats were housed in alternate light/dark conditions (light on, 7:00 AM, light off, 7:00 PM). Corticosterone was determined by radioimmunoassay from blood samples that were obtained by tail clip at 4-h intervals. Pinealectomized animals have shown significant increase of corticosterone levels at 7:00 AM, 11:00 AM and 7:00 PM in comparison with 2-month-old intact rats. There were no differences in serum corticosterone rhythm between 24-month-old and pinealectomized animals. Twelve-month-old rats have shown significant increase of corticosterone levels at 7:00 and 11:00 AM in comparison with 2-month-old animals. The age-associated increase of serum corticosterone and the similarity between serum corticosterone circadian rhythm in aged and pinealectomized animals suggest that an age-related decrease in melatonin production [Reiter et al., 1981] may contribute to age related changes of hypothalamic-pituitary adrenal axis regulation.

Dopaminergic modulation of aldosterone secretion in the rat.

Abstract: The dopamine antagonist metoclopramide (MCP) has been shown to acutely stimulate aldosterone secretion in vivo. To determine whether a dopaminergic mechanism is involved in the regulation of aldosterone secretion, we examined the effect of minipump infusion of MCP (iv) and/or angiotensin II (All; sc) upon plasma aldosterone, adrenal capsular All receptors, and 18-hydroxylase activity in rats maintained on high sodium intake. During normal sodium intake, plasma aldosterone was elevated from 8.3 ± 1.3 to 35.4 ± 3.2 μg/dl after 2-day infusion of a nonnatriuretic dose of All (25 μg/min) and to 15.0 ± 1.8 ng/dl after the infusion of 1.2 Mg/min MCP. All receptors were unchanged by MCP infusion, and rose from 1014 ± 98 to 1638 ± 98 fmol/mg after All infusion. During high sodium intake, the infusion of either All or MCP alone produced no change in plasma aldosterone or All receptors. However, after simultaneous infusion of All and MCP, plasma aldosterone rose from 4.5 ± 1.2 to 32.5 ± 2.7 ng/dl, All receptors incr...

Mechanisms of adrenocortical depression during Escherichia coli shock.

Abstract: • The response of the adrenal cortex to corticotropin during sepsis is variable. We have previously demonstrated a significant decrease of corticosterone production by rat adrenocortical cells in response to corticotropin stimulation after incubation with septic shock plasma (SP) as compared with control plasma (CP). We have studied the mechanisms of this depression. The following defects were demonstrated. (1) Cells bound less radioiodinated corticotropin analog after SP treatment (2.9±0.4 femtomoles/50 μg DNA) than after CP treatment (6.4±0.3 fmole/50 μg DNA). (2) Cyclic adenosine monophosphate (cAMP) production was less after SP treatment (59.3 ± 4 pmole per 10 5 cells per two hours) compared with CP treatment (110.3±11.3 pmole per 10 5 cells per two hours). (3) Exogenously added dibutyryl cAMP was unable to correct the defect in corticosterone production after SP treatment (4.96±0.7 μg/24 hr) as compared with CP treatment (6.99±0.5 μg/24 hr). Our studies suggest this defect is located in the synthesis of pregnenolone from cholesterol. These mechanisms may be responsible for the low cortisol levels previously observed in humans during septic shock. ( Arch Surg 1984;119:145-150).

Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography

Abstract: Nuclear localization of tritiated aldosterone in the CNS was studied in rats by numerical evaluation of silver grains, deposited over neuronal cell nuclei in thawmounted autoradiograms, and compared with the localization obtained after prior administration of a 100-fold excess of radioinert aldosterone, corticosterone or 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Corticosterone and 18-OH_DOC completely prevented nuclear localization in most regions examined. However, in contrast to pretreatment with aldosterone, pretreatment with corticosterone and 18-OH-DOC did not completely prevent the concentration of radio-activity in the cell nuclei of the indusium griseum. Traces of radioactivity were, furthermore, retained in areas CA1 and CA2 and the dentate gyrus in rats exposed to corticosterone, but not to 18-OH-DOC, prior to [3H]aldosterone. A similar profile of silver grain distribution to that noted with aldosterone was found for corticosterone except that with tritiated corticosterone the most intense concentration of radioactivity occurred in hippocampal areas CA1 and CA2 and not in the indusium griseum. Prior administration of excess deoxycorticosterone acetate abolished nuclear accumulation of tritiated corticosterone. Dihydrotestosterone, on the other hand, failed to compete with tritiated corticosterone at a dose 200-fold in excess of the tritiated steroid. We conclude that (1) a receptor readily shared by aldosterone, corticosterone, 18-OH-DOC and DOC, but not by dihydrotestosterone, is widely distributed throughout the CNS, (2) a receptor shared by aldosterone and 18-OH-DOC, but not by corticosterone may be present in hippocampal areas CA1 and CA2, (3) that both these as well as the receptor accepting dihydrotestosterone can be located within the same cell.