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PubMed1975

Relationship between ACTH release and corticosterone binding by the receptor sites of the adenohypophysis and dorsal hippocampus following infusion of corticosterone at a constant rate in the adrenalectomized rat.

The amount of corticosterone bound to proteins in the adenohypophysis and dorsal hippocampus was studied concurrently with the plasma ACTH concentration in 4-week adrenalectomized male rats under steady-state conditions achieved by infusing the steroid at a constant rate for 45 min. Corticosterone binding was measured by gel chromatography on Sephadex LH-20, using a TE buffer containing 0.4 m NaCl. No saturation was observed in whole homogenates and supernatants with increasing plasma corticosterone concentrations. However, corticosterone binding by the pituitary and by one of two types of hippocampal receptors evidenced saturation within our range of corticosterone infusion rates, indeed. Scatchard plots allowed us to distinguish two types of binding sites in the hippocampus. The first, saturated at a low corticosterone concentration has an association constant of 3.0 times 10-8 M-1 with a number of binding sites estimated at 150 times 10- minus 15 mol/mg protein, whereas the second is associated with non-specific binding. The adenohypophysis shows only one kind of binding site with an association constant of 3.6 times 10-8 m- minus 1 and a number of sites estimated at 989 times 10- minus 15 mol/mg protein. A suggestive relationship was observed between ACTH inhibition by corticosterone and saturation of the pituitary binding sites. Our data are consistent with the possible involvement of corticosterone binding by specific sites in the negative feedback regulation of ACTH release.

Adrenalectomy↗

PubMed1987

Effect of corticosterone on circulating concentrations of corticosterone, prolactin, thyroid hormones and somatomedin C and on fattening in broilers selected for high or low fat content.

Daily changes in the concentrations of plasma corticosterone, prolactin, thyroid hormones and somatomedin C were measured in 28-day-old fat and lean lines of broilers produced by selection for high and low concentrations of very low density lipoproteins (VLDL). The effects of daily injections of corticosterone on the concentrations of these hormones and on fattening were compared in the two lines. The selection procedure had no effect on the concentrations of any of the hormones. However, daily rhythms in concentrations of plasma corticosterone, tri-iodothyronine (T3) and prolactin were less often observed in the fat line than in the lean line. No differences were seen between lines in the daily rhythms in plasma thyroxine (T4) and somatomedin C. Daily injections of 2500 micrograms corticosterone/kg body weight, in both lines, depressed mean concentrations of plasma prolactin, T3 and somatomedin C and body weight. This dose of corticosterone also increased abdominal fat pad and liver weights expressed as a percentage of body weight. The liver and fat pad responses to 2500 micrograms corticosterone in both lines were greater when the steroid was injected at the end rather than towards the beginning of the 14-h daily photoperiod. There was no difference between the lines in the fattening response to corticosterone. Lower doses of 100 and 500 micrograms corticosterone per day did not induce fattening or affect concentrations of plasma prolactin. They did, however, depress concentrations of plasma T3. Concentrations of plasma T4 were increased in both lines treated with 2500, but not with 100 or 500 micrograms corticosterone, towards the beginning of the daily photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed2001

Fecal corticosterone reflects serum corticosterone in Florida sandhill cranes.

Florida sandhill cranes (Grus canadensis pratensis) were conditioned to confinement 6 hr/day for 7 days. On day 8, each bird's jugular vein was catheterized, blood samples were drawn, and each crane was confined for 6 hr. Using a randomized, restricted cross-over design, cranes were injected intravenously with either 0.9% NaCl solution or ACTH (cosyntropin; Cortrosyn; 0.25 mg). During the 6 hr of confinement, fecal samples (feces and urine) were collected from each of five cranes immediately after defecation. Individual fecal samples were collected approximately at hourly intervals and assayed for corticosterone. We showed previously that serum corticosterone did not vary significantly following saline injection, but peaked significantly 60 min after ACTH injection. Maximal fecal corticosterone concentrations (ng/g) were greater (P < 0.10; median 1087 ng/g) following ACTH stimulation compared to maximal fecal corticosterone concentrations at the end of acclimation (day 7; median 176) and following saline treatment (median 541). In cranes under controlled conditions, fecal corticosterone concentration reflects serum corticosterone levels, fecal corticosterone, Grus canadensis pratensis, sandhill cranes, serum corticosterone levels.

Adaptation, Physiological↗

PubMed1975

Sexual differences in hepatic metabolism and intracellular distribution of corticosterone studied by pulse labeling with (1,2,6,7-3H)corticosterone.

The subcellular distribution of corticosterone and its metabolites in liver was studied 5, 30, and 90 min after injection of (1,2,6,7-3/)corticosterone in adult male and female rats that were adrenalectomized or hypophysectomized: 5 min after administration of isotope, the adrenalectomized male rats contained ten times as much labeled unconjugated corticosterone, 5alpha-dihydrocorticosterone, and 3alpha- and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one on the nuclear fraction than the corresponding female rats. The metabolites of corticosterone in the soluble fraction of liver from adrenalectomized females occurred as about 90 per cent steroid monosulfates and disulfates already 5 min after administration of isotope. In contrast, the soluble fraction of liver from males contained only 38 per cent labeled monosulfate 5 min after injection of (1,2,6,7-3H)corticosterone. The individual labeled metabolites from the different subcellular fractions were identified by thin-layer and radio-gas chromatography. The major metabolites found in the female were mono- and disulfurylated 3alpha,11beta,15,21-tetrahydroxy-5alpha-pregnan-20-one, 3alpha,15,21-trihydroxy-5alpha-pregnane-11,20-dione, and 3alpha,11beta,21-trihydroxy-5alpha-pregnan-20-one. The predominant metabolites in the male were 5alpha-pregnane-3alpha(and 3beta),11beta,20beta,21-tetrol and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one which mainly occurred as mono- and disulfates. Hypophysectomized female rats showed a corticosterone metabolite pattern with almost no 15-hydroxylated metabolites but with large amounts of isomers of pregnane-3,11beta,20beta,21-tetrol, i.e., a "masculinized" pattern. It is concluded that hepatic intracellular metabolism and transport of corticosterone in vivo in rats are characterized by large sexual difference which are at least partly under hypophyseal control.

Adrenalectomy↗

PubMed2000

Corticosterone facilitates saccharin intake in adrenalectomized rats: does corticosterone increase stimulus salience?

Unlike normal rats, adrenalectomized rats do not voluntarily drink sweet saccharin solutions. To test whether this is a function of corticosterone in the circulation, and if corticosterone also increases the impetus for drinking saccharin after a period of withdrawal, we performed the following experiments. Young male rats were sham adrenalectomized (sham) or adrenalectomized (ADX); the ADX rats were provided with subcutaneous pellets containing (percent replacement of corticosterone, %B) 0%B, 15%B, 30%B or 100%B. Sham and ADX rats were immediately provided with saline (0.5%) and saccharin (2 mM) bottles in their home cages. Saccharin was allowed for 4 days on, 3 days off, 4 days on, 3 days off and a final day on, over the 15 days experiment. The dose of corticosterone determined both how much saccharin was voluntarily drunk by the ADX rats and the degree of overshoot after days off. Corticosterone also determined energy balance of the groups of ADX rats. The 30%B pellets restored food intake, body weight gain, insulin and caloric efficiency to the normal levels observed in sham rats. White fat depot weights and uncoupling protein concentration in brown adipose tissue were restored to sham levels by 100%B, suggesting that these variables which depend on activity in the sympathetic nervous system require considerable glucocorticoid receptor occupancy. We conclude that corticosterone increases the willingness to ingest sweetened water in a unimodal, dose-related manner, while moderate doses of corticosterone restore energy balance.

Adrenalectomy↗

PubMed2005

Japanese quail selected for high plasma corticosterone response deposit high levels of corticosterone in their eggs.

Poor habitat quality or body condition often correlates with high responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis rather than with elevated baseline levels of glucocorticoids. We hypothesized that, for egg-laying vertebrates, high responsiveness of the HPA axis would correspond to high concentrations of corticosterone in yolk. We tested the prediction that Japanese quail (Coturnix coturnix japonica) selected for high plasma corticosterone response to brief immobilization (HS quail) would lay eggs with higher yolk corticosterone concentrations than birds selected for low response (LS quail). Quail from both lines were left undisturbed, outside of the stressors associated with daily management, before a first round of egg collection. In a second experiment, quail of both lines were experimentally stressed during the week before egg collection. In both cases we found quail from the HS line to lay eggs with significantly higher yolk corticosterone concentrations than quail of the LS line. After exposure to added experimental stressors, the line difference was more pronounced (increasing from 62% to 96%). There was no line difference in concentrations of yolk testosterone. Our results suggest that (1) genetic differences underly differences in the transfer of maternal corticosterone to yolk and (2) females may be able to control deposition of corticosterone into yolk through a mechanism independent of baseline corticosterone titers.

Animals↗

PubMedDate not supplied

Effect of cannulation surgery and restraint stress on the plasma corticosterone concentration in the rat: application of an improved corticosterone HPLC assay.

PURPOSE: Stress increases plasma corticosterone concentration in rats. We studied the time-course of plasma corticosterone post jugular vein cannulation, a potential stress producing process, and after 1 h restraint stress using an improved assay. Current HPLC methods for corticosterone analysis require long extraction times with large volumes of solvent. METHODS: Adult male, Sprague-Dawley rats were used. Tail vein blood samples were collected from uncannulated rats (n=4). Other rats were cannulated in the right jugular vein, allowed to recover overnight and assigned to days 1, 2, 3 or 4 groups (n=4-6/group). Blood was sampled before and after exposure to 1 h of restraint stress. Plasma was separated and extracted with 5 mL ethyl acetate (betamethasone as internal standard), and then the extract was washed with sodium hydroxide (0.1 M) and water. After evaporation of ethyl acetate, the residue was dissolved in mobile phase (acetonitrile-water-acetic acid-TEA, 22:78:0.1:0.03, v/v) and injected into an isocratic HPLC consisting of a 10 cm C18 column, and UV detector at 254 nm. RESULTS: The minimum quantifiable concentration was 10 ng/mL of corticosterone based on 0.5 mL plasma. The standard curve was linear over the concentration range of 10-500 ng/mL. The extraction efficiency was 84-87%. The coefficient of variation for intra-day and inter-day precision was <10% with <8% error. Plasma corticosterone before cannulation (74 +/- 17 ng/mL) and those measured daily before restraint stress were not significantly different from one day to another (day 1, 60 +/- 21; day 2, 59 +/- 39, day 3, 45 +/- 23, and day 4, 41 +/- 8 ng/mL). Exposure to restraint stress elevated corticosterone (day 1, 122 +/- 33; day 2, 82 +/- 23; day 3, 148 +/- 33; and day 4, 134 +/- 20 ng/mL). Except on day 2, all concentrations were significantly elevated as compared to the pre-stress levels. CONCLUSIONS: Corticosterone concentrations were stable after jugular vein cannulation, and were increased by restraint stress. The present assay is a more convenient method as compared to those previously reported.

Animals↗

PubMed1988

Hormonal changes following tumor transplantation: factors increasing corticosterone and the relationship of corticosterone to tumor-induced anti-inflammation.

EL-4 lymphoma cells transplanted to syngeneic C57BL/6J mice induced a biphasic decrease in inflammation and a bi-phasic increase in serum levels of corticosterone. In addition, this tumor altered serum levels of 3 other hormones, resulting in a biphasic decrease in insulin, an early decrease in prolactin, and a terminal severe deficiency in thyroxine. Early changes occurred 16 to 48 hr after tumor transplantation and were of variable duration, while late-phase defects developed during the last few days of life. Soluble factors associated with tumor growth may mediate certain hormonal changes since serum levels of corticosterone increased and insulin decreased following injection of tumorous ascites into normal mice. Further, injection of cell-free tumor culture supernatants increased corticosterone levels. Hormonal changes following injection of soluble factors occurred after a delay of 16 hr indicating that the factors acted indirectly. Surgical adrenalectomy blocked the corticosterone increase induced by tumor transplantation or ascites injection and eliminated the anti-inflammatory effect of tumor transplantation while significantly decreasing the effect associated with injection of tumorous ascites. Thus, the physiologically induced increase in serum levels of corticosterone reached anti-inflammatory levels. Further, elevated levels of corticosterone are a major contributing factor to anti-inflammation induced by tumorous ascites injection and constitute the principal mechanism of anti-inflammation following tumor transplantation.

Animals↗

PubMed1989

Effect of corticosterone infusion on plasma corticosterone concentration, antibody production, circulating leukocytes and growth in chicken lines selected for humoral immune responsiveness.

The effect of corticosterone on antibody production was studied in chicken lines selected for humoral immune response. 2. Twelve cockerels (33 days old) from lines selected for high or low antibody responses after immunisation with sheep red blood cells (SRBC) were implanted with mini-infusion pumps delivering corticosterone or vehicle continuously for 14 d. 3. Three days after implantation, the chickens were immunised intramuscularly with 0.25 ml packed SRBC. Blood samples were taken before implantation, before immunisation and 3, 5, 7 and 11 d after immunization. 4. Corticosterone infusion induced higher plasma corticosterone concentrations and heterophil/lymphocyte ratios than infusion of vehicle only. Growth was considerably depressed and relative weights of the thymus, bursa of Fabricius and spleen were less in the corticosterone-infused chickens. 5. An effect of corticosterone on antibody production could not be demonstrated, and differences between selection lines were unaffected.

Animals↗

PubMed1985

Down-regulation of neural corticosterone receptors by corticosterone and dexamethasone.

Stress or elevated corticosterone titers can reduce the concentration of corticosterone receptors in the brain. We demonstrate that corticosterone and the related glucocorticoid, dexamethasone, induce different anatomical patterns of such 'down-regulation'. Corticosterone administration reduces receptor number in the hippocampus, particularly the CA1 and CA2 pyramidal cell fields, but nowhere else in the brain or pituitary. In contrast, equivalent dosages of dexamethasone down-regulate pituitary, amygdaloid and hypothalamic corticosterone receptor numbers. These different anatomical profiles of sensitivity to down-regulation appear due to differential access of the two steroids to the receptor pools.

Amygdala↗

PubMed1993

Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance.

In order to test the hypothesis that maternal corticosterone influences hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and behaviors related to it, we induced a moderate increase in maternal plasma level of corticosterone by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day after delivery to weaning. Our previous experiments have shown that this procedure produces plasma levels of the hormone in the range of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8 micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml in the pups at 10 days of lactation). Adrenal weights were slightly and temporarily decreased by treatment in both mothers and offspring. Only the male progeny was investigated in this study. Corticosterone-nursed rats had significantly less corticosterone and ACTH in basal conditions and after a 2 min restraint stress at 3 months of age, and showed better performances at weaning and at 1, 2 and 3 months of life in the Morris water maze. Our results demonstrate that a moderate increase in maternal corticosterone during lactation influences the activity of HPA axis and improves spatial learning ability of the adult offspring.

Adrenal Glands↗

PubMedDate not supplied

Extraction of corticosterone from cell homogenates and subcellular fractions of the rat adrenal cortex. III. ACTH-induced temporal subcellular redistributions of steroid precursors to corticosterone.

Cholesterol, pregnenolone, progesterone, 11-deoxycorticosterone (11-DOC) and corticosterone were quantitated in subcellular fractions isolated from in vivo adrenocorticotropin (ACTH)-stimulated rat adrenal zona fasciculata/reticularis. Six adrenal subcellular fractions separated by discontinuous sucrose gradient centrifugation (lipid, 0.125 M sucrose, cytosolic, microsomal, mitochondrial and nuclear) were extracted with alkaline ether/ethanol and assayed by high pressure liquid chromatography (HPLC). Lipid fractions contained the major cholesterol stores, while most pregnenolone and progesterone was found in lipid, microsomal and mitochondrial fractions. The 0.125 M sucrose and cytosol fractions together contained approximately 75% of the total 11-DOC and corticosterone. The five steroids were only present in small amounts in organelle fractions containing steroidogenic enzymes. Homogenate and lipid fraction cholesterol decreased between 10 and 15 min and again 30 min after ACTH injection. In the homogenate, lipid, microsomal and mitochondrial fractions, pregnenolone and progesterone were increased after ACTH injection; peak pregnenolone and progesterone concentrations were often measured in adrenal gland sucrose, cytosolic, microsomal and mitochondrial fractions 15 to 20 min after rats were injected with ACTH. Although ACTH increased 11-DOC and corticosterone in all but the mitochondrial and nuclear fractions, the sucrose, cytosolic and microsomal 11-DOC, and cytosolic corticosterone increased most dramatically. In many fractions, peak 11-DOC and corticosterone concentrations were most often observed between the 10 and 15 min periods and again at 30 min.

Adrenal Cortex↗

PubMed2006

Development of stress reactivity in white-crowned sparrow nestlings: total corticosterone response increases with age, while free corticosterone response remains low.

Activation of the adrenocortical response to stress during development can have fundamental consequences over the lifetime of the organism; as such, many organisms are less responsive to stress during critical developmental periods. In this study, we evaluated stress reactivity in nestling white-crowned sparrows, examining corticosterone and binding globulin levels in response to both restraint stress and ACTH challenge. Restraint stress induced a significant corticosterone response in both 4 to 6- and 7 to 9-day-old nestlings, but not in the youngest group (1-3 days); this non-significant increase in corticosterone in the youngest birds resembles the mammalian hyporesponsive period, wherein young animals are resistant to most stressors. Binding globulin levels appear to extend this period of low reactivity: when free corticosterone levels were calculated, only the oldest age group (7-9 day) showed a significant response to restraint. ACTH challenge data revealed that all ages of white-crowned sparrow nestlings responded to exogenous ACTH treatment with significant elevation of corticosterone, although early-stage nestlings did not reach adult levels of response.

Adrenal Cortex↗

PubMed1975

Estimation of aldosterone, 11-deoxycorticosterone, 18-hydroxy-11-deoxy-corticosterone, corticosterone, cortisol and 11-deoxycortisol in human plasma by gas-liquid chromatography with electron capture detection.

A method for determining the plasma concentrations of six major corticosteroids, aldosterone, 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), corticosterone, deoxycorticosterone (DOC), cortisol and 11-deoxycortisol using gas-liquid chromatography with electron capture detection is described. Esterification of suitable derivatives of these compounds with heptafluorobutyric anhydride (HFB) allowed detection of quantitities of steroid, ranging from 0-3 pg for androstenetrione HFB (from cortisol) to 2-3 pg for corticosterone HFB. No detectable reagent blank was obtained for any compound when water was used instead of plasma and this was also the case when plasma from an adrenalectomized subject was analysed, with the exception of 18-OH-DOC where a reproducible but negligibly small blank occurred. Coefficients of variation for replicate determinations ranged from 8% for corticosterone to 17% for aldosterone. Concentrations in a series of normal human plasma samples were as follows: aldosterone, 4-0- 18-0 ng/100 ml; 18-OH-DOC, 20-16- ng/ml; corticosterone, 0-08 - 0.-80 mug/100 ml; DOC, 2-8 - 16-0 ng/100 ml; cortisol, 2-5 - 10-0 mug/100 ml; and 11-deoxycortisol, 40-0 - 400-0 ng/100 ml. When seven normal subjects were treated with dexamethasone concentrations of DOC, cortisol and 11-deoxycortisol fell to below the limit of the normal range, those of 18-OH-DOC and corticosterone were at the lower end of the normal range while the concentration of aldosterone was not significantly affected.

Adrenal Cortex Hormones↗

PubMed1987

Enhanced corticosterone-binding capacity in plasma after stimulation of the rat adrenal cortex: the possibility of a simultaneous release of protein and corticosterone.

Exposure of rats to either footshock or handling stress produced a significant increase in both plasma corticosterone concentration and specific binding capacity. Non-specific binding was eliminated using the synthetic glucocorticoid, dexamethasone. The increase in both plasma corticosterone and specific binding capacity was biphasic following exposure to footshock. Adrenalectomy and pretreatment with betamethasone abolished both phases of the enhanced binding capacity and plasma steroid concentration. Intraperitoneal injection of ACTH (1-24) in animals pretreated with betamethasone resulted in a biphasic rise in plasma concentrations of corticosterone but only the initial increase in binding capacity. Dissociation constant (Kd) values, determined by Scatchard analysis, for adrenalectomized and betamethasone-pretreated animals were 546 and 556 pmol/l respectively. These values were significantly different from the Kd in animals with functional adrenals (631 pmol/l). The results are discussed in the light of a possible specific corticosteroid-binding globulin (CBG) like binding protein of adrenal origin released in conjunction with corticosterone. This binding protein has a lower affinity for corticosterone and a shorter half-life than CBG.

Adrenal Cortex↗

PubMed1978

Cannabinoid effects on plasma corticosterone and uptake of 3H-corticosterone by mouse brain.

The effects of three cannabinoids, 11-hydroxy-delta9-tetrahydrocannabinol (11-HO-delta9-THC), delta9-THC and cannabinol (CBN), ranging in behavioral activity from high to low, were studied on two aspects of pituitary--adrenal function. Plasma corticosterone levels were used as an index of adrenocorticotropic hormone (ACTH) release. All three cannabinoids elicited an increase in plasma corticosterone elvels in a manner similar to their behavioral potency. These cannabinoids also elicited an increase in the concentration of 3H-corticosterone taken up by the brains of adrenalectomized mice in a manner similar to their potency in elevating plasma corticosterone levels. The significance and possible underlying mechanism of the apparent correlation resulting between these effects and the behavioral effects of cannabinoids are discussed.

Adrenalectomy↗

PubMed1977

Progesterone in the uterus. VIII. Uptake of corticosterone and incorporation of progesterone under concurrent injection of corticosterone into rat uterus.

A study of the subcellular distribution of radioactivity in rat uterus after injection of labelled corticosterone showed that the radioactivity was observed in all fractions from 5 min. to 120 min. A maximum uptake was observed 10 min. after application of the labelled steroid. Competitive uptake of radioactive progesterone and unlabelled corticosterone was assayed 10 min. after injection of the hormone mixture. The ratio between radioactive progesterone and unlabelled corticosterone was 1:1 and 1:2 (moles:moles), respectively. Compared with control experiments with rats which had received radioactive progesterone alone, the results gave evidence that progesterone found in all subcellular fractions and in the total homogenate was not depressed by unlabelled corticosterone. However, unlabelled progesterone reduced the tritiated progesterone in uterine tissue. This observation demonstrates that the uptake of progesterone by rat uterus is specific.

Animals↗

PubMedDate not supplied

Radioimmunoassay of total and free corticosterone in rat plasma: measurement of the effect of different doses of corticosterone.

A radioimmunological method was developed for determining total and free corticosterone in rat plasma. This method was used to determine the dose-response curve of corticosterone and to measure the elimination and study the half-lives of total and free corticosterone in rat plasma with a dose of 5 mg/kg. The elimination with a dose of 5 mg/kg, when drawn on the half-logarithmic scale, formed a straight line. The half-lives for total and free corticosterone were 25 and 15 min, respectively.

Animals↗