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PubMed1984

Extraction of corticosterone from cell homogenates and subcellular fractions of the rat adrenal cortex. II. ACTH-induced changes in subcellular corticosterone.

Zona fasciculata-reticularis subcellular structures were implicated in corticosterone transport and secretion by noting changes in subcellular corticosterone during a 30-min period following ACTH stimulation. Six decapsulated adrenal homogenate subcellular fractions separated by gradient centrifugation were characterized cytochemically and morphologically. Predominant components in each of six fractions were: floating lipid droplets, 0.125 M sucrose (no organelles), cytosol (0.25 M sucrose supernatant with 0.25-1.2 micron electron dense granules), microsomes (interface between 0.5 M and 1.1 M sucrose layers), mitochondria (boundary between 1.1 M and 2.2 M sucrose layers) and nuclei (centrifuge pellet). Whole glands and most subcellular fractions showed peak corticosterone levels 10 to 15, and 30 min after stimulation. Sucrose and cytosolic fractions contained about 75% of the total corticosterone, responded to stimulation most significantly, and were rich in protein. In these two fractions only cytosol contained structures; these consisted of 0.15-1.2 micron electron dense granules.

Adrenal Cortex↗
PubMed1989

Developmental changes in the corticosterone response to corticotrophin and in the adrenal corticosterone content of rapid and slow growing strains of chickens (Gallus domesticus).

1. The high sensitivity of the immature domestic fowl to corticotrophin (ACTH) has been confirmed. The minimal effective dose was age-dependent, and decreased from 2 IU/kg BW in 1-d-old chicks to 0.4 IU/kg BW in 12-d-old chicks. 2. Increasing doses of ACTH evoked similar maximal corticosterone responses but the time to return to basal values increased with increasing dose of ACTH in both a broiler and layer strain. 3. Maximal corticosterone responses to ACTH occurred earlier in hatched chicks compared with embryos, and were delayed in embryos and young chicks of the layer strain compared to those of the broiler strain. 4. Strain differences in basal concentrations of corticosterone as well as in the response to ACTH occurred at a time when there were differences in the corticosterone content of the adrenals.

Adrenal Glands↗
PubMed1983

Daily fluctuations of peripheral metabolism of corticosterone in male Japanese quails: a dynamic approach to the development of plasma corticosterone daily rhythm.

An ultradian rhythm was found in the daily variation of the parameters concerning the peripheral metabolism of corticosterone in sexually mature male Japanese quails. The period of this rhythm was eight hours; three peaks and minima were found in the daily fluctuation of metabolic clearance rata and an antiphysed rhythm in the biological half-life as well as in tetrahydrocorticosterone/corticosterone conversion rata. The findings emphasize the importance of the peripheral metabolism in developing of corticosterone plasma levels; and analyze the circadian rhythm of corticosterone plasma level as a result of secretion rate and peripheral disappearance.

Animals↗
PubMed1995

Interdependence of corticosterone and thyroid hormones in toad larvae (Bufo boreas). II. Regulation of corticosterone and thyroid hormones.

Typically, the role of corticosterone(B) in metamorphosis is considered secondary to that of thyroid hormone, with B having only enhancing effects. In the current study, we demonstrate that the relationship between the thyroid hormones and B is much more complex and that thyroxine (T4) may depend on B for some of its functions. Tadpoles of the western toad (Bufo boreas) were treated with various combinations of corticosterone (B), thyroxine (T4), triiodothyronine (T3), a goitrogen (thiourea; Thio), and a corticoid synthesis inhibitor (metyrapone; MTP). Hormones were extracted from individual tadpoles and whole-body hormone levels determined by radioimmunoassay. B-treatment decreased the ratio of T4 to T3, suggesting that B increased the conversion of endogenous T4 to T3. In addition, B-treatment in combination with T4 resulted in high whole body-levels of T3. B also caused a decrease in whole body-thyroid hormone levels (T4 and T3), suggesting negative feedback on the hypothalamo-pituitary-thyroid axis and T3 had a similar effect, decreasing whole body-T4 levels. T4-treatment, but not T3, increased whole body-B levels and MTP-treatment in combination with T4 prevented the stimulatory effect of T4 on B production. MTP-treatment alone blocked all steroid metabolism of [3H]progesterone by the inter-renal in vitro, and lowered whole body-B levels three-fold in vivo. Thio-treatment reduced thyroid hormone levels and also resulted in decreased B. Finally, we suggest that these results demonstrate a system in which T4 may regulate its own potency: increasing T4 stimulates B production, which increases the conversion of T4 to its more active form T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Synthesis of 7 alpha- and beta-carboxymethyl derivatives of cortisol, corticosterone, deoxycorticosterone and cortisone. Immunogenic properties of cortisol, corticosterone and deoxycorticosterone derivatives.

7 alpha- and 7 beta-Carboxymethylderivatives of cortisol, corticosterone and deoxycorticosterone have been synthetized. After coupling to bovine serum albumin, they were used to elicit antibodies in rabbits. Highly specific antisera were obtained which may possibly be used for a direct radioimmunoassay of these steroids in human and rodent plasma. In the case of the derivatives of cortisol and corticosterone and stereoisomery of the coupling had an effect on the affinity and the specificity of the antisera. In all immunized rabbits the antisera obtained with the 7 alpha-derivative had a higher affinity and a narrower specificity than the antiserum obtained with the 7 beta-derivative.

Antibody Affinity↗
PubMed1988

HPLC separation of corticosterone metabolites and its use in following corticosterone metabolism and transport in the isolated rat hepatocyte.

Incubating isolated rat hepatocytes with tritium labelled and unlabelled corticosterone at 37 degrees C resulted in the rapid appearance of at least nine corticosterone metabolites. A quick, relatively easy, and quantitative high performance liquid chromatographic (HPLC) method was used to separate these metabolites and follow their rate of appearance both intra- and extracellularly. We found different intra- and extracellular amounts of each metabolite at a particular time and this suggested that some metabolites were more available for transport than others.

Animals↗
PubMed1984

Time course of plasma corticosterone, 18-hydroxycorticosterone and aldosterone concentrations following CRF administration in the rat. A phase of corticosterone inhibition.

Synthetic ovine CRF (8 micrograms/rat) injected intravenously in nembutal anaesthetized rats increased not only plasma ACTH and corticosterone but also aldosterone and 18-hydroxycorticosterone concentrations. The maximum elevation occurred 30 min after oCRF administration. 2 h and 4 h after injection the hormone concentrations declined and after 6 h the corticosterone and 18-hydroxycorticosterone values were lower than the corresponding controls. At this time aldosterone remained slightly elevated and ACTH unchanged. 24 h after oCRF injection no difference between the control and oCRF treated animals were evident.

18-Hydroxycorticosterone↗
PubMed2003

Short-term fasting affects locomotor activity, corticosterone, and corticosterone binding globulin in a migratory songbird.

Unpredictable events such as severe storms lead to an increase in circulating corticosterone (CORT) in breeding birds. This increase is often accompanied by elevations in foraging and irruptive behavior. We were interested in determining if acute food restriction (such as might occur during inclement weather) is a sufficient cue to elicit an increase in locomotor activity, increase CORT secretion, and/or decrease circulating levels of corticosterone binding globulin (CBG) in white-crowned sparrows (Zonotrichia leucophrys gambelii). Male Z.l. gambelii were housed individually in environmental chambers on long days (LD 20:4) to simulate breeding season daylength. Birds were fed ad libitum, and on select days, food was removed 2 h after lights on (fasted treatment), or was removed and replaced (control). We analyzed CORT and CBG levels after 1, 2, 6, 22 (lights on), and 23 h under fasted and control conditions. We also measured activity during the 23-h experiment. Activity levels were increased under fasted conditions during the daytime relative to control conditions, but activity levels did not differ between treatments during the night. Fasting as little as 1, 2, and 6 h significantly increased total CORT levels above baseline (control), although after 22 h, total CORT levels under fasted conditions matched those under control conditions. Plasma CBG decreased after the 22-h fast, and remained low after the 23-h fast. This change was sufficient to significantly elevate free CORT levels in fasted birds relative to ad libitum food conditions, despite the lack of difference in total CORT levels.

Animal Migration↗
PubMed1984

Circadian fluctuations in plasma corticosterone, corticosterone-binding activity and total protein in male rats: possible disruption by serial blood sampling.

Male rats were bled serially every 6 h for 48 consecutive hours. Plasma so obtained was assayed for corticosterone (B), corticosterone-binding activity (CBA) and total plasma protein (TPP). Although the averaged data indicated a significant circadian rhythm in plasma B, inspection of the circadian changes in individual animals showed that 40% had irregular or aberrant patterns of plasma B. Additionally, circadian fluctuations in plasma CBA were approximately 3-fold lower in magnitude than previously reported, and there was no significant circadian change in TPP. Running wheel activity during the 48 h blood sampling period decreased by over 50% indicating that the serial sampling procedure caused disruption of the activity cycle. However, the majority of wheel-running activity occurred during the dark portion of the day-night cycle. Because circadian fluctuations in plasma proteins, including corticosteroid binding globulin (CBG), may be directly related to changes in locomotor activity, it is suggested that the attenuation of circadian changes in CBA and TPP were due to disruption of the daily cycle of locomotor activity. The abnormal circadian patterns in plasma B observed in some animals also may have been caused by disruption of the activity cycle in spite of the fact that the rats did not appear to be stressed as evidenced by concentrations of plasma B that were well within the normal range.

Animals↗
PubMed1992

Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and age-related changes in hippocampal type I and type II corticosteroid receptor binding capacity in young and aged, handled and nonhandled rats.

Basal corticosterone (B) levels increase with age in the rat, a result of decreased negative-feedback inhibition of hypothalamic-pituitary-adrenal (HPA) activity. Postnatal handling increases CNS negative-feedback sensitivity and appears to attenuate some of the changes occurring in the HPA axis in later life. In the experiments described here, we have examined basal HPA function in young (6-8 months) and old (22 months), handled (H) and nonhandled (NH) rats in relation to changes in corticosteroid receptor binding. Among young animals, there were no group differences in basal adrenocorticotropin (ACTH) or B levels at any point in the diurnal cycle. In contrast, plasma ACTH and B levels during the PM phase were significantly higher in old NH animals in comparison to old H animals and to both groups of young animals. The H and NH groups did not differ in in vivo adrenal responsiveness to exogenous ACTH. As expected, ACTH sensitivity was greater in all groups during the PM phase and in general, old animals showed a greater response to ACTH regardless of the treatment group. There were no differences across the groups in AM plasma corticosterone-binding globulin (CBG) levels. However, during the PM phase of the cycle, CBG levels were significantly lower and the percentage of B in the free form was significantly higher in the old NH animals. As expected, levels of free B during the PM phase of the cycle were significantly higher in the old NH animals. Thus, there is a significant increase in the PM corticoid signal in the old NH animals that occurs as a function of elevated B and decreased CBG levels; these age-related changes in basal HPA activity were not seen in the old H animals. Type I (mineralocorticoid-like) receptor binding in the hippocampus did not differ as a function of handling and was significantly reduced with age in both H and NH animals. Type II (glucocorticoid) receptor binding decreased as a function of age in both H and NH animals, but was consistently higher in the H animals. There were no differences in type II receptor binding in the hypothalamus or pituitary as a function of age or handling. These data suggest that the increase in basal HPA activity occurring in aged rats is largely restricted to the dark phase of the cycle and is attenuated by postnatal handling, a treatment that increases hippocampal type II corticosteroid receptor binding.

Adrenocorticotropic Hormone↗
PubMed1995

Interdependence of corticosterone and thyroid hormones in larval toads (Bufo boreas). I. Thyroid hormone-dependent and independent effects of corticosterone on growth and development.

In a previous study (Hayes et al. [1993] J. Exp. Zool., 266:206-215), we demonstrated that exogenous corticosterone (B) inhibited growth, and had varied effects on development and metamorphosis in the toad (Bufo boreas). The current study determined the relation between the actions of B and thyroid hormones on body growth (length and weight), tail growth and reduction (length and height), rear leg growth and differentiation, and foreleg emergence (FLE). Thiourea (Thio; a goitrogen) and metyrapone (MTP; a glucocorticoid synthesis inhibitor) were used to determine the role of endogenous hormones in growth and development. These inhibitors were also used in various combinations with the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), to determine the extent to which B's actions depend on the thyroid hormones. B was ineffective at inducing tail reduction (length and height) in the presence of Thio, but B enhanced the effects of both thyroid hormones, suggesting that the actions of B on the tail were dependent on thyroid hormones. B inhibited body growth even in the presence of Thio, but did not enhance thyroid hormone's inhibition of growth. B alone stimulated foreleg emergence (FLE) and enhanced thyroid hormone's activity on FLE when B and the thyroid hormones were given in combination, but did not induce FLE in the presence of Thio. B stimulated rear leg development, but not in the presence of Thio, suggesting that this effect was due to interactions with thyroid hormones. Furthermore, MTP antagonized the stimulatory effect of T4 on rear leg development, suggesting that endogenous B also interacted with exogenous thyroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal pyramidal cells: acute high corticosterone administration increases action potential number.

The hypothalamic-pituitary-adrenocortical (HPA) axis controls the levels of plasma corticosterone (CT) in the rat and the levels of cortisol in man. CT is important in maintaining homeostasis and regulating energy production. Homeostasis is maintained by basal activation of the hippocampal-HPA axis. In response to stress CT secretion is increased. CT activation of receptors in the hippocampus provides feedback inhibition of the HPA axis to return the system to basal activity. There are two types of CT receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). CT has a 10-fold higher affinity for MR than GR. Normal basal levels of CT occupy the majority of the MR. During the diurnal surge of CT and following the presentation of a stressful stimulus, the MR and GR are both maximally occupied. To begin to understand how CT influences the hippocampal-HPA axis, intracellular recording techniques in the hippocampal brain slice preparation were used to determine how high concentrations of CT may alter cell characteristics and/or evoked synaptic activity. Two treatment groups were used, i.e., adrenalectomized (ADX) and ADX with CT pellet replacement (ADX+CT) that produced plasma blood levels equal to that seen in a normal rat in the morning. Acute administration of 100 nM CT decreased action potential threshold and the number of action potentials elicited by a depolarizing current pulse in cells from both the ADX and ADX+CT treated rats. The amplitude of the evoked excitatory postsynaptic potentials (EPSP) or inhibitory postsynaptic potentials (IPSP) declined in cells recorded from ADX animals and ADX rats acutely treated with high concentrations of CT (ADX/CT).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Corticosterone implants in the paraventricular nucleus inhibit ACTH and corticosterone responses and the release of corticotropin-releasing factor following neural stimuli.

Experiments were conducted on the possible role of corticosterone (CS), at the level of the paraventricular nucleus of the hypothalamus (PVN) and dorsal hippocampus (D.HIPP), in the negative feedback effects following neural stimuli. In rats with bilateral PVN cholesterol (CHO) implants, acoustic and photic stimuli caused a significant rise in serum CS and ACTH and depletion of median eminence (ME) CRF-41 content. CS PVN implants have prevented the rise in serum CS, ACTH and ME CRF-41 depletion. Bilateral CHO or CS implants in the D.HIPP did not modify the responses of the hypothalamo-pituitary-adrenal axis to the above neural stimuli. In PVN CS-implanted rats, i.v. injection of CRF-41 increased serum CS similar to that observed in PVN CHO-implanted animals. These data are discussed in view of previous experiments on corticosteroid implants in the brain. It is concluded that CS PVN implants, by acting possibly via type II hypothalamic receptors, have prevented the release of ME CRF-41 following neural stimuli and consequently the secretion of ACTH and CS.

Acoustic Stimulation↗
PubMed1994

A comparison of the effects of repeated stressor exposures and corticosterone injections on plasma cholesterol, thyroid hormones and corticosterone levels in rats.

Persistently elevated serum cholesterol (CHOL) levels have been observed in rats given repeated stressor exposures and fed a normal laboratory diet. To determine the relative contribution of persistent hormone changes in the hypothalamic-pituitary-adrenal (HPAA) and thyroid axes to persistent stress-induced CHOL elevations, the present experiment assessed the contribution of persistently elevated corticosterone (CORT) from both endogenous and exogenous sources. Groups of rats were exposed for 7 days to stress sessions (7DS; 40, 2mA tailshocks given over 2 h each day), CORT injections (CI; 10 mg/l ml vehicle/day) or vehicle injections (VI; sesame oil), or served as noninjected, undisturbed controls (CON). In addition, another group of rats were adrenalectomized (ADX). Basal blood samples were drawn for CORT determination on the 1st, 4th, 7th, and 8th experimental days. The blood samples from the 8th day, 22 h after the last stress session or injection were also assayed for CHOL, T3 and T4. The basal CORT levels of both 7DS and CI rats were elevated on the 4th and 7th experimental days. Contrary to expectations, 7 daily exposures to the stress regimen did not persistently alter plasma CORT, CHOL, T3 or T4 levels. The CI rats did exhibit elevated CORT on the 8th experimental day which was accompanied by elevated CHOL levels and suppressed T4 levels. However, elevated CHOL levels were also found in ADX rats and these elevations were accompanied by suppressed T3 levels. These data suggest that persistent CORT elevations are not necessary for persistent plasma CHOL elevations after stressor exposure, but further research is necessary to clarify the role of the HPAA and thyroid axes in stress-induced plasma CHOL elevations.

Adrenalectomy↗
PubMed2005

Corticosterone inhibits feather growth: potential mechanism explaining seasonal down regulation of corticosterone during molt.

Corticosterone (CORT) is seasonally modulated in many passerines, with plasma CORT concentrations lowest during the prebasic molt when all feathers are replaced. To explain why, we proposed that the birds downregulate natural CORT release during molt in order to avoid CORT's degradative effects on proteins and its inhibition of protein synthesis. If CORT exerted these effects during molt, it could slow protein deposition during feather production and potentially result in a longer period of degraded flight performance. To test this hypothesis, either empty or CORT-filled silastic implants were inserted into captive European starlings (Sturnus vulgaris) and white-crowned sparrows (Zonotrichia leucophrys) undergoing induced (feather replacement after plucking) and natural molts. We then measured the rate of feather re-growth by regularly measuring the length of primary, secondary, and tail feathers. CORT implanted birds showed a significantly decreased rate of feather growth compared to control animals. Basal CORT concentrations of induced molt and non-molting birds were also compared but no difference was noted. The results suggest a tradeoff; a complete set of new feathers may be more important to the survival of a bird than the ability of CORT to respond maximally to a stressor.

Animals↗
PubMed2001

Exposure to repeated low-level formaldehyde in rats increases basal corticosterone levels and enhances the corticosterone response to subsequent formaldehyde.

Low-level exposure to volatile organic compounds may produce symptoms in humans reporting multiple chemical sensitivity (MCS) through altered hypothalamic-pituitary-adrenal (HPA) axis functioning. We determined whether repeated formaldehyde (Form) exposure would alter corticosterone (CORT) levels in a rat model of MCS. Male Sprague-Dawley rats were given acute chamber exposures to Air or Form (0.7 or 2.4 ppm), and trunk blood was collected 20 or 60 min later. All groups showed increased CORT levels above naïve basal levels at 20 min and a return to baseline by 60 min, with no differences between treatment groups. The second experiment examined the effect of repeated Form exposure (1 h/day x 5 days/week x 2 or 4 weeks) on basal CORT levels and after a final challenge. Basal CORT was increased above naïve values after 2 week exposure to Air or 0.7 ppm Form. By 4 week, CORT levels in the Air group returned to naïve values, but remained elevated in the 0.7 ppm Form group. There were no differences in basal CORT levels among either 2.4 ppm exposed groups. After a final Air or Form challenge, the 2 and 4 week Air and 0.7 ppm Form groups had elevated CORT levels similar to their acute response, while the 2 and 4 week 2.4 ppm Form groups had elevated CORT levels compared to their acute response, indicating enhanced reactivity of the HPA axis to subsequent Form. These findings suggest that altered HPA axis functioning occurs after repeated low-level Form exposure, and may have implications for mechanisms mediating MCS in humans.

Animals↗
PubMed1998

Decreased apparent affinity of corticosterone for colonic crypt glucocorticoid receptors is dependent on the cellular milieu and is distinct from corticosterone metabolism.

[3H]Steroid binding in intact colonic crypt cells and cytosol was compared to determine if 11beta hydroxysteroid dehydrogenase (11betaHSD) activity modulates access of corticosterone (B) to both glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Cytosol from non-adrenalectomized rat colonic crypt cells showed no 11betaHSD activity, and B bound with high affinity to both MR (Kd=0.47+/-0.03 nM; Bmax=177+/-34 fmol/mg protein) and GR (Kd=4.5+/-0.3 nM; Bmax=279+/-40 fmol/mg protein). In contrast, intact colonic crypt cells incubated with 25-30 nM [3H]B for 90 min converted 62% of B to 11-dehydrocorticosterone, with little binding to MR (14+/-3 fmol/mg protein) and GR (22+/-5 fmol/mg protein). When 11betaHSD activity was inhibited with carbenoxolone, and the same concentration of [3H]B used, binding of [3H]B to MR increased 10-fold to 122+/-12 fmol/mg protein, not significantly different from MR levels in colonic crypt cytosol. In contrast, [3H]B binding to GR in intact cells increased only 1.6-fold to 36+/-9 fmol/mg protein, significantly less than to GR in cytosol (212+/-24 fmol/mg protein). Scatchard analysis showed both lower levels of GR and an apparently lower affinity for [3H]B in colonic crypt cells (Kd=31+/-3 nM; Bmax=130+/-21 fmol/mg protein) compared with cytosol (Kd=4.5+/-0.3 nM; Bmax=279+/-40 fmol/mg protein. [3H]Dexamethasone similarly showed an apparently lower affinity and capacity for GR (Kd=8.8+/-1.3 nM; Bmax=232+/-32 fmol/mg protein) in intact cells compared with cytosol (two separate determinations, Kd=2.6 and 2.9 nM; Bmax=369 and 300 fmol/mg protein). In contrast, [3H]aldosterone displayed similar affinity and capacity for MR in both intact cells (Kd=2.0 nM; Bmax=121 fmol/mg protein) and cytosol (Kd=1.5 and 1.4nM; Bmax=115 and 93 fmol/mg protein). These findings demonstrate not only that 11betaHSD modulates binding to both MR and GR in colonic crypt cells, but also that an additional mechanism(s) operating in whole cells but not in cytosol selectively reduces the affinity and capacity of colonic GR for both natural and synthetic ligands.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

Amplification of mineralocorticoid activity of aldosterone by 18-hydroxy-corticosterone and 18-hydroxy-19-nor-corticosterone in adrenalectomized rats.

A combination of aldosterone (1 micrograms) with either 18-OH-corticosterone (1 micrograms) or 18-OH-19-norcorticosterone (1 micrograms) injected to adrenalectomized rats indicated an amplification of mineralocorticoid activity as expressed by Na/K ratio in urine. Without aldosterone their mineralocorticoid potency was negligible.

18-Hydroxycorticosterone↗