Showing papers on "Corticosterone published in 1982"

In Vivo Corticotropin-Releasing Factor-Induced Secretion of Adrenocorticotropin, β-Endorphin, and Corticosterone*

Abstract: A 41-residue peptide purified as a corticotropin-releasing factor/beta-endorphin-releasing factor (CRF) in vitro was tested for its ability to stimulate the secretion of ACTH, beta-endorphin, and corticosterone in three animal groups: 1) unanesthesized rats bearing indwelling venous cannulae, 2) rats pretreated with chloropromazine plus morphine sulfate plus pentobarbital (CPZ-MS-Nb, and 3) rats with hypothalamic deafferentiations in the frontal and lateral retrochiasmatic areas. In all three bioassays iv administration of 0.1-10 micrograms CRF elicited a dose-related increase in plasma ACTH and beta-endorphin values over a 5- to 15-min period. Corticosterone secretion was also elevated but responded maximally with all doses of CRF tested. Pretreatment of CPZ-MS-Nb animals with 20 micrograms dexamethasone 4 h before assay abolished the CRF-induced hormone secretion. These data suggest that CRF may play a physiological role in the regulation of the hypothalamic-pituitary-adrenal axis.

Endocrine Responses of White-Crowned Sparrows to Environmental Stress

Abstract: --Field and laboratory investigations were conducted to assess the effects of selected stressors on White-crowned Sparrows (Zonotrichia leucophrys gambelii and Z. 1. pugetensis). Within a few minutes after capture during the nonbreeding winter phase, the birds' plasma corticosterone increased, whereas their already low levels of luteinizing hormone (LH) and dihydrotesterone (DHT) declined further. In contrast, in the summer, or breeding phase, corticosterone levels increased much more slowly (sometimes not at all in females) during the first hour after capture. Plasma levels of LH in breeding birds were unaffected by capture and handling, as were levels of DHT in males and estrogen in females. In some cases, however, circulating levels of testosterone declined in males. In photostimulated, caged, male Z. 1. gambelii circulating levels of corticosterone, LH, and DHT appeared to be unaffected by ambient temperatures between 50 and 320C, but the level of testosterone was significantly depressed at 320C. Capture, transport for 250 km, and subsequent caging of male and female Z. 1. gambelii in autumn and winter within 24 h increased plasma corticosterone, and decreased LH and DHT. As the birds acclimated to captivity, a decrease in levels of corticosterone was followed by transient elevations of LH and DHT after which concentrations of these hormones stabilized at capture levels. Males transferred from outdoor aviaries and held one, two, or three per cage on short days also developed elevated concentrations of corticosterone and depressed levels of LH and DHT. Corticosterone decreased within two weeks in birds held one or two per cage, and within three weeks in those housed three per cage. As corticosterone levels decreased, transient increases occurred in LH and DHT, with the highest levels in birds held three per cage. For more than half a century feral passerine birds have been used in investigations in both laboratory and field. Recently techniques have been developed to examine changes in endocrine status and in condition of the reproductive system of individually marked breeding birds in the field (Wingfield and Farner 1976, 1977, 1978a, b). However, relatively little consideration has been given to the development and effects of stress under the conditions of investigation. Although capture, handling, laparotomy, transport, and confinement in captivity are presumably stressful, we know of no attempt as yet to assess the role of these procedures as stressors in feral avian species. Such assessments are obviously critical for interpreting data on endocrine and gonadal function derived from such species in both the field and laboratory. In addition, they should provide insights into the underlying mechanisms of responses and adaptations of natural populations to stressful disturbances or alterations of the environment. Using a system first described six years ago (Wingfield and Farner 1976), we have assessed the effects of selected assumed stressors on the plasma concentrations of corticosterone, luteinizing hormone, and sex steroid hormones in White-crowned Sparrows (Zonotrichia leucophrys). MATERIALS AND METHODS

Virus-Induced Corticosterone in Hypophysectomized Mice: A Possible Lymphoid Adrenal Axis

Abstract: Infection of hypophysectomized mice with Newcastle disease virus caused a time-dependent increase in corticosterone and interferon production. Prior treatment with dexamethasone completely inhibited the virus-induced elevation in corticosterone concentration, but did not significantly alter the interferon response. Lymphocytes appear to be the most likely source of an adrenocorticotropin-like substance that is responsible for the increased corticosterone, since spleen cells from the virus-infected, but not from control or dexamethasone-treated, hypophysectomized mice showed positive immunofluorescence with antibody to adrenocorticotropin-(1-13 amide). Thus the adrenocorticotropin-like material and interferon appear to be coordinately induced the differentially controlled products of different genes. These findings strongly suggest the existence of a lymphoid-adrenal axis.

Primary cortisol resistance in man. A glucocorticoid receptor-mediated disease.

Abstract: We have studied a man suspected of having primary cortisol resistance on the basis of high 24-h mean plasma cortisol levels (27.4 micrograms/dl) and no stigmata of Cushing's syndrome. His son had slightly elevated 24-h mean plasma cortisol levels (9.9 micrograms/dl; normal 7.52 micrograms/dl). Both had high plasma protein unbound cortisol and increased urinary free cortisol. Plasma ACTH concentration was high, and both were resistant to adrenal suppression by dexamethasone. The father appeared to have mineralocorticoid excess resulting in hypertension, hypokalemia, and metabolic alkalosis. This was found to be due to markedly elevated plasma levels of deoxycorticosterone and corticosterone. The son, who was normotensive, had mildly increased plasma corticosterone and normal deoxycorticosterone levels. To study the apparent end-organ resistance to cortisol, we examined the glucocorticoid receptor in the white cells and fibroblasts of these patients. In both tissues, using both whole cell and cytosol assays, the glucocorticoid receptor was found to have reduced affinity for dexamethasone. In the cytoxol assays, a reduced receptor number was found as well. We conclude that cortisol resistance is a rare familial syndrome owing to an abnormal glucocorticoid receptor with a decreased affinity for cortisol.

Specificity of the adrenal steroid receptor system in rat hippocampus

Abstract: The binding properties of the adrenal steroid receptor system in rat hippocampus were analyzed in vitro in cytosol binding experiments and in vivo with cell nuclear uptake studies. All experimental animals were adrenalectomized 3 days previously for removal of endogenous adrenal steroids. Scatchard analysis of [3H]corticosterone and [3H]dexamethasone in vitro binding in cytosol gave linear plots. Binding parameters for [3H]corticosterone-labeled sites were a maximal binding capacity (Bmax) of 424 fmol/mg protein and a Kd of 3.4 nM and for [3H] dexamethasone-labeled sites, a Bmax of 507 fmol/mg protein and a Kd of 5.0 nM. Scatchard analysis of [3H]aldosterone binding showed two populations of binding sites: one with high affinity (Kd= 2.6 nM) and low capacity (Bma = 80 fmol/mg protein) and the other with low affinity (Kd = 29.8 nM) and higher capacity (Bmax = 347 fmol/mg protein). Inclusion in the incubation medium of 0.6-fold excess unlabeled corticosterone or of 100-fold excess of the “pure” glucocortico...

Regulation of glucocorticoid receptors in brain by corticosterone treatment of adrenalectomized rats.

Abstract: Binding of (3H)-corticosterone in cytosol of hippocampus and hypothalamus has been measured in adrenalectomized (ADX) rats in the presence or absence of corticosterone replacement therapy (suspended shortly before receptor analysis). Corticosterone pellet implantation into female rats or oral corticosterone administration in salinized drinking water given to males for 3 weeks reduced (3H)-corticosterone binding by half in the hippocampus. This reduction was observed whether corticosterone or dexamethasone was employed as competitor to determine nonspecific binding, thus eliminating transcortin as the cause of the corticosterone effect on binding. Scatchard analysis of binding data revealed that the reduction was mostly due to decreased number of receptors. Animals pretreated with corticosterone had a reduction in thymus weight, indicating further the biological effectiveness of the treatment. Further, serum corticosterone in ADX rats pretreated with corticosterone (but with therapy suspended for 24 h) was very low and similar to that of untreated ADX rats. Uptake studies after injection of (3H)-corticosterone intravenously into ADX rats showed that the injected hormone was absent from blood and brain tissues 1 day later, ruling out (in addition to the measurement of serum corticosterone) that the reduction in binding was due to occupation of receptor sites by exogenous corticosterone remaining after withdrawal from therapy. It is suggested that down-regulation of glucocorticoid receptors in brain follows the chronic corticosterone administration. These data are discussed in relation with evidence for down-regulation of other classes of steroid receptors in several tissues, and the consequence that changes in receptor binding in brain may have on the feedback mechanism of corticoids at the central level.

Pituitary-adrenal function in rats chronically exposed to cold.

Abstract: Exposure to cold for 2 weeks was used to assess the effects of a sustained stimulus on pituitary-adrenal function in male rats. The diurnal peak in plasma and adrenal corticosterone was advanced by 4 h during the first 24 h of exposure to cold but returned to its usual time (2000 h) by the next day. Plasma ACTH and corticosterone levels were generally greater at all times during the 24-h cycle in animals exposed to cold for up to 2 weeks, with the greatest increase occurring consistently at the time of peak. When rats exposed to cold for 1 week were returned to a normal 24 C environment, plasma corticosterone tended to increase. Plasma ACTH and plasma and adrenal corticosterone responses to a superimposed acute provocative stimulus (ip saline injection) were faster, greater, and more sustained in rats exposed to cold for 3 or 7 days. Similarly, the compensatory adrenal hypertrophy response to unilateral adrenalectomy was greater in cold-exposed rats. Such animals were also more resistant to pituitary-adrenal suppression by prednisolone. In contrast, there was no change in the sensitivity of the adrenal to exogenous ACTH. The results suggest that chronic exposure to cold causes a sustained activation of central mechanisms that regulate pituitary ACTH secretion as well as extra-pituitary mechanisms that regulate adrenal size; it reduces the effectiveness of negative feedback mechanisms, but does not alter those involved in the regulation of adrenal rhythmicity or adrenal sensitivity to ACTH.

Long-term effects of fetal ethanol exposure on pituitary-adrenal response to stress ☆

Abstract: Pregnant female rats were fed either a 5.0–5.5% w/v ethanol-containing liquid diet ad lib or pair-fed the isocaloric control diet during gestation weeks 2 and 3. At 75–105 days of age, female offspring of the ethanol-treated dams showed significantly greater corticosterone responses than pair-fed- or normally-derived offspring to the stress of cardiac puncture or of noise and shaking, while pituitary-adrenal responses to exposure to a novel environment, cold or 2–3 days of fasting were normal. Adrenal sensitivity to ACTH in dexamethasone-suppressed adult offspring was unaffected by the prenatal treatment. The results demonstrate that fetal ethanol exposure enhances adult pituitary-adrenal responses to certain stressors, including alcohol as demonstrated previously, and suggest that the long-term effects may be mediated by developmental actions of alcohol on central neural mechanisms involved in the regulation of this neuroendocrine system.

Corticosterone: a critical factor in an opioid form of stress-induced analgesia

Abstract: The finding that some opioid-mediated forms of stress-induced analgesia are antagonized by hypophysectomy and dexamethasone has led to the suggestion that beta-endorphin, released from the pituitary, may mediate these analgesic reactions. "Long-term analgesia" (an opioid-mediated form of stress-induced analgesia), which is blocked by dexamethasone and hypophysectomy, was also blocked by adrenalectomy and reinstated with corticosterone therapy. Corticosterone is proposed to play a permissive role in long-term analgesia and to be a critical hormone mediating this phenomenon.

Radioimmunoassay (RIA) of serum corticosterone in rats.

Abstract: A radioimmunoassay for corticosterone was developed and characterized using corticosterone antiserum (377, Niswende) and a simple ethanol extraction procedure. The antiserum appeared to be highly specific fo corticosterone. Intraassay variability was 3.67 +- 0.75% (mean +- SE) at 50 pg of corticosterone; interassay variability with a mean value of 51.15 pg was 6.98 +- 1.01%. Assay sensitivity was 9.48 +- 0.60 pg. Utilizing this assay, serum obtained from adrenalectomized and adrenalectomized-ovariectomized rats yielded lower corticosterone values than serum from intact or ovariectomized rats. Intact females had lower corticosterone values than intact males. Rats exposed to elevated temperature (32.5/sup 0/) displayed significantly (P < 0.001) elevated plasma corticosterone levels (48.48 +- 4.37 ..mu..g/100 ml) compared to control (24.5/sup 0/) animals (21.31 +- 2.02 ..mu..g/100 ml). The high specificity, sensitivity, precision, recovery level, and ease of this technique make it useful for the study of either serum or plasma corticosterone.

Stress-induced inhibition of the plasma corticosterone response to a subsequent stress in rats: a nonadrenocorticotropin-mediated mechanism.

Abstract: The present study was designed to define further the relationships between ACTH and corticosterone secretion after repeated administration of a discrete restraint stress in rats. The possibility that plasma ACTH and corticosterone responses to stress may be modified by prior exposure to stress was examined in male rats using a 2-min restraint stress. The peak plasma ACTH response to a single restraint stress occurred at 2.5–5 min after the onset of the stress, and plasma ACTH returned to the basal concentration by 30 min. The plasma corticosterone concentration after this stress peaked at 15–30 min and returned to the control range by 60–90 min. The time courses of the plasma ACTH and corticosterone responses to restraint stress after administration of three prior stresses at 90-min intervals were similar to those after a single stress. Stressinduced increments in plasma concentrations of ACTH and corticosterone were similar in rats that received either a single restraint stress or as many as seven stress...

Effect of corticosterone treatment on muscle protein turnover in adrenalectomized rats and diabetic rats maintained on insulin.

Abstract: The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [14C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.

Corticotropin releasing factor (CRF)-stimulation test in normal controls and patients with disturbances of the hypothalamo-pituitary-adrenal axis

Abstract: Intravenous application of 100 µg synthetic ovine corticotropin releasing factor (CRF) led to stimulation of ACTH-secretion in nine normal controls, with a maximum 30 min after CRF. Cortisol, corticosterone, cortisone and 11-deoxycortisol increased with a maximum at 60 min after CRF, whereas no rise was seen in aldosterone, 11-deoxycorticosterone, 17-α-hydroxyprogesterone, progesterone, DHEA-S and testosterone. The specificity of CRF-stimulation was also shown by unchanged TSH, LH, FSH, hGH, prolactin and thyroid hormone levels, als well as unchanged insulin and gastrin levels. No serious side-effects were observed during the test period and afterwards.

The Control of Steroidogenesis by Human Fetal Adrenal Cells in Tissue Culture. IV.The Effects of Exposure to Placental Steroids

Abstract: The effect upon steroidogenesis of adding various steroids produced by the placenta was studied in short term cultures of human fetal adrenal cells. The addition of high concentrations (103 ng/ml) of estrone or estriol inhibited the production of cortisol, but only the former elicited a parallel increase in dehydroepiandrosterone (DHA) production. Estradiol was effective in inhibiting Δ4-3-ketosteroid production at concentrations of 10-100 ng/ml, levels which approach those found in the fetal circulation, while DHA production was increased at concentrations of 1 eg/ml. The addition of progesterone (4 eg/ml) to the medium caused increased production of cortisol and corticosterone, but had no effect on DHA production. Pregnenolone (4)eg/ml) increased the basal production of DHA and slightly impaired both basal and ACTH-stimulated aldosterone production, but had no effect on cortisol production. The data demonstrate that of the many fetal and placental factors which have been studied to date, only ACTH and e...

Diurnal rhythm of total and free concentrations of serum corticosterone in the rat.

Abstract: Daily variations in serum concentrations of total and free corticosterone and corticosteroid-binding globulin (CBG) were determined at 4 h intervals in male rats maintained on a 12:12 h light/dark cycle (lights on at 05.00 h). Total corticosterone concentrations exhibited a classical rhythm with peak values occurring at the onset of dark (17.00 h). Serum CBG concentrations displayed daily fluctuations but these appeared to be non-rhythmic in nature. The % free corticosterone exhibited a diurnal rhythm with peak values occurring during the dark phase. When absolute concentrations of free corticosterone were calculated, the profile could be superimposed on that of total corticosterone with the zenith at the onset of the dark phase (17.00 h) and the nadir coinciding with the onset of light (05.00 h). These data suggest that the primary determinant of the rhythm in free corticosterone concentrations is the daily rhythm in total corticosterone.

Adrenal involvement in the expression of delayed-type hypersensitivity to SRBC and contact sensitivity to DNFB in stressed mice.

Abstract: The stress of immobilization has previously been demonstrated to suppress delayed-type hypersensitivity (DTH) responses to an iv injection of sheep erythrocytes (SRBC). However, immobilization enhances contact sensitivity reactions to the cutaneous application of 2,4-dinitro-l-fluorobenzene (DNFB). In the following experiments, both adrenalectomy and the corticosteroid inhibitor, metyrapone, were used to evaluate the influence of corticosterone on the expression of these cell-mediated immune events in stressed mice. Adrenalectomy and metyrapone after induction of the immune response abolished the suppression of DTH to SRBC that was observed in immobilized, control animals. In contrast, the immobilization-induced increase in contact sensitivity to DNFB was still observed after adrenalectomy or metyrapone treatment. Similar results were observed when mice were given metyrapone or adrenalectomized before sensitization. These data indicate that adrenal corticosteroids are involved in the stress-induce...

Effects of adrenalectomy and corticosterone administration on hypothalamic obesity in rats.

Abstract: The present experiment was designed to assess the role of adrenal hormones in hypothalamic hyperphagia and obesity. Ventromedial hypothalamic (VMH) or sham lesions were produced either 15 days before or after adrenalectomy (ADX) or sham adrenalectomy in rats in a completely counterbalanced design (experiment 1). Body weight and food intake were recorded for 30 days after the second surgery. Adrenalectomy in obese VMH animals eliminated all excess weight gain and decreased food intake to below the level of all control groups. VMH lesions in ADX animals did not produce the characteristic weight gain associated with ventromedial hypothalamic damage, and this group was not significantly different from animals with sham lesions in body weight or food intake. In experiment 2, the administration of corticosterone resulted in a marked increase in the rate of weight gain in ADX-VMH animals, and the withdrawal of the hormones was followed by weight loss. It is concluded that adrenal glucocorticoid hormones are necessary for the development and maintenance of VMH hyperphagia and obesity.

Ornithine decarboxylase induction by glucocorticoids in brain and liver of adrenalectomized rats.

Abstract: Ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, was measured in the brain and the liver of adrenalectomized rats after an acute S.C. treatment with glucocorticoids. The effects of corticosterone and dexamethasone were compared in three brain areas, the cerebral cortex, hippocampus, and cerebellum. These structures have similar concentrations of cytosolic glucocorticoid receptor, as measured by an in vitro exchange assay using a specific glucocorticoid ligand, [3H]RU 26988, but contain different amounts of mineralocorticoid receptor. Corticosterone and dexamethasone increased ODC activity in the liver and brain areas in a dose dependent manner, dexamethasone being more active than corticosterone in all tissues. Moreover, estradiol, progesterone, and testosterone were inactive. Aldosterone, at high doses, increased brain ODC activity. Glucocorticoids, selected for their weak binding, or lack of binding to the mineralocorticoid receptor, were tested and found to be highly active in inducing brain and liver ODC, thus showing that ODC induction by steroids is specific for glucocorticoids. These results are among the first to suggest biochemically a central action of glucocorticoids following an acute treatment and confirm that the brain is a glucocorticoid target organ.

Characterization of an Early Inhibitory Effect of Glucocorticoids on Stimulated Adrenocorticotropin and Endorphin Release from a Clonal Strain of Mouse Pituitary Cells

Abstract: The ability of glucocorticoid steroid hormones to inhibit release of ACTH and endorphin has been studied in the mouse pituitary tumor cell strain, AtT-20/ D l6v. Inhibition of release of both peptides was first detectable at 30 min (to 80–90% of control release) and was maximal (30–50% of control) by 3–4 h of pretreatment with dexamethasone (1 × 10-6 M). Glucocorticoids did not consistently affect basal hormone release, but they inhibited release stimulated 4-to 8-fold by hypothalamic extract, phorbol esters, or 8-Br-cAMP but not high K+-stimulated release. The inhibitory effect was glucocorticoid specific and dose dependent with ED50S for dexamethasone, corticosterone, and cortisol close to their reported KdS for binding to the cytoplasmic glucocorticoid receptor. Inhibition of release was blocked by cycloheximide (1 × 10-5 M), suggesting that protein synthesis was required. Experiments were performed to determine the site of action of glucocorticoids. Steroid pretreatment for up to 6 h had no effect on ...

Glucocorticoid Influence on Tyrosine Hydroxylase Activity in Mouse Locus Coeruleus during Postnatal Development

Abstract: Administration of corticosterone (10 mg/kg, ip, twice daily for 3 days) to mice during the second week of postnatal development led to an increase of tyrosine hydroxylase (TH) activity in the locus coeruleus, but not in the substantia nigra. The corticosterone effect was observed only transiently during this developmental period. Tritiated corticosterone can bind to a cytosol fraction prepared from mouse locus coeruleus, with a specific binding capacity of 110 fmol/mg protein. There is a correlation between the ability of various steroids to increase TH activity and their binding to the cytosol glucocorticoid receptor. Cortexolone and progesterone, two antiglucocorticoids that can bind to the cytosol receptor, were found to abolish the effect of corticosterone in increasing TH activity. It appears that the noradrenergic neurons in the locus coeruleus may be target cells for glucocorticoids, and that the glucocorticoid effect on TH may be a receptor-mediated mechanism.

Catecholamine turnover in the brain and the regulation of luteinizing hormone and corticosterone in starved male rats

Abstract: The effect of starvation was studied in male Wistar rats. After only 2 days of food deprivation, LH concentrations in serum are greatly suppressed, while a significant increase in plasma corticosterone occurs after 5 days' starvation. The noradrenaline and dopamine turnover in the basal hypothalamus is decreased after 2 days. The catecholamine turnover is also reduced in the preoptic area, and in the median eminence. Injection of the catecholamine precursor L-dopa (100 mg/kg) can prevent the increase of plasma corticosterone, but not the decrease of LH. The alpha-agonist clonidine (150 micrograms/kg), but neither the beta-agonist salbutamol (0.5 mg/kg), nor the dopamine agonist apomorphine (1.0 mg/kg) can prevent the starvation induced corticosterone increase. The decrease of plasma LH is not influenced by the dopamine or noradrenaline agonists. From these data, it appears that a decreased activity of noradrenergic neurons may be responsible for the corticosterone increase in the plasma of starved rats.