Glucocorticosteroid Levels Research Articles

Alterations of Glucocorticosteroids Thyroid Hormones Leptin and Endothelins Threat of Cardiovascular Disease in Diabetes

Background: The cardiovascular diseases are phenomenon or circumstances that affect the structures as well as function of the heart. Aim: The level of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiovascular subjects was determined in Owerri, Imo state. Method: A total of 100 subjects within the age 35-65 years were recruited for this study. The study consists of 50 subjects who were diagnosed of cardiac disorders and 50 were apparently healthy individuals who served as controls subjects of the same age bracket. The levels of glucocorticosteroids, thyroid hormones, leptin, and endothelins were analysed using ELISA technique. Data was assessed using SPSS version 20, the mean value with P˂ 0.05 was considered statistically significant. Results: The result revealed that the levels of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiovascular disorder were significantly increased when compared with control subjects. Conclusion: The increased serum level of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiac malfunction subjects may contribute some risk factors in patients with cardiac dysfunction and in people living with diabetes.

Antidepressant-like effects of albiflorin involved the NO signaling pathway in rats model of chronic restraint stress.

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE) and dopamine (DA) in the hippocampus and increased the level of brain-derived neurotrophic factor (BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal (HPA) cascade, reduced the level of NO and cGMP in serum and inhibited the overexpression of 5-HT2AR mRNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors. These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.

Acupuncture improves hippocampal apoptosis state by reducing expression of ROS and Cytochrome C and Caspase-3 in Chronic Restraint Stress Rats

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg−1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE) and dopamine (DA) in the hippocampus and increased the level of brain-derived neurotrophic factor (BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal (HPA) cascade, reduced the level of NO and cGMP in serum and inhibited the overexpression of 5-HT2AR mRNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors. These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.

Effect of methylprednisolone on mammalian neuronal networks in vitro.

Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP on cultured neuronal networks, followed by a shut-down of electrical activity using the microelectrode array technique.

Nest Predation and Circulating Corticosterone Levels within and among Species

Variation in the risk of predation to offspring can influence the expression of reproductive strategies both within and among species. Appropriate expression of reproductive strategies in environments that differ in predation risk can have clear advantages for fitness. Although adult-predation risk appears to influence glucocor - ticosteroid levels, leading to changes in behavioral and life-history strategies, the influence of offspring-predation risk on adult glucocorticosteroid levels remains unclear. We compared total baseline corticosterone concentrations in Gray-headed Juncos (Junco hyemalis dorsalis) nesting on plots with and without experimentally reduced risk of nest predation. Despite differences in risk between treatments, we failed to find differences in total baseline cor - ticosterone concentrations. When we examined corticosterone concentrations across a suite of sympatric species, however, higher risk of nest predation correlated with higher total baseline corticosterone levels. As found previ- ously, total baseline corticosterone was negatively correlated with body condition and positively correlated with date of sampling. However, we also found that corticosterone levels increased seasonally, independent of stage of breeding. Nest predation can alter the expression of birds' reproductive strategies, but our findings suggest that total baseline corticosterone is not the physiological mechanism regulating these responses.

Adrenal Function in the Mongolian Gerbil (Meriones Unguiculatus): Influence of Confinement Stress upon Glucocorticosteroid, Progesterone, Dehydroepiandrosterone, Testosterone and Androstenedione Plasma Levels, Adrenal Content and In-Vitro Secretion

The pattern of adrenal steroid secretion and the response to confinement stress were investigated in male Mongolian gerbils (Meriones unguiculatus). Steroid levels of glucocorticosteroids (GC), progesterone (P), dehydroepiandrosterone (DHEA), testosterone (T) and androstenedione (A) in plasma, adrenal tissue and superfusates of adrenals superfused in-vitro were measured by radioimmunoassay. The sensitivity of the assay systems and the low cross-reactivity of the antisera used allowed the determination of steroid levels in small samples (5-200 microliters), without prior chromatography. GC plasma levels were much higher than values of P, DHEA, T or A (176.7, 2.4, 3.3, 2.6 and 2.8 ng/ml, respectively). Confinement stress resulted in a significant increase of GC and DHEA plasma levels; similarly, adrenal content of GC, DHEA and P was markedly increased. In contrast, the applied stress factor had no significant effects on either plasma levels of P, T or A or on adrenal T or A content. Compared to plasma levels or adrenal content, amounts of steroids secreted from adrenals superfused in-vitro were very low (GC: 57.1, P: 2.1, DHEA: 23.0, T: 1.8, A: 3.0 pg/mg/min, respectively). Confinement stress significantly stimulated GC, P and DHEA secretion in-vitro but had no effects on T or A release. The secretion of GC, P, DHEA and T, but not of A was significantly increased by in-vitro stimulation with 0.01-10.0 mIU (1-24) ACTH. Interestingly, the amounts of GC and P, and of GC and DHEA secreted from incubated adrenal slices stimulated with (1-24) ACTH and from adrenals of controls and stressed gerbils superfused in-vitro were significantly correlated. By measuring steroid plasma levels and profiles of steroids secreted from adrenocortical and testicular tissue it now seems possible to characterize in more detail the effects of chronic intermittent stress upon the adrenalgonadal axis and the possible interrelationship between glucocorticosteroid and androgen secretion, especially in small laboratory animals from which only limited amounts of blood can be obtained repeatedly.

In vitro effects of dexamethasone on mouse ovarian function and pre-implantation embryo development

The effect of dexamethasone (5–80 μg/ml) on ovarian function and embryo development was studied in mice. The follicle bio-assay revealed no effects of DEX up to 40 μg/ml on folliculogenesis and oogenesis, whereas 80 μg/ml hampered follicle differentiation and oocyte maturation. Androgen, estrogen and progestin secretion patterns were strongly impaired at all doses levels. However, the ovulation-induced progesterone increase indicating that the steroid pathway was activated in presence of DEX. Applying the oil-free mouse embryo assay no alteration of DEX on the first cleavage stages were observed whereas blastocyst rate decreased from 20 μg/ml DEX onwards, and hatching capacity was already impaired in presence of 10 μg/ml DEX. In conclusion, steroidogenesis was affected from 5 μg/ml onwards and the minimum effective inhibitory dose was set at 10 μg/ml for early embryo development. Based on these in vitro findings, physiological or therapeutic levels of glucocorticosteroids are unlikely to affect female fertility.

The role of adrenal corticosteroids in induction of micronuclei by morphine

It has previously been shown that morphine can increase the frequency of micronucleated splenocytes when administered to mice, but not when cells are exposed to the opiate in vitro. Morphine treatment is also known to increase circulating levels of glucocorticosteroids, which have been reported to produce genetic damage in vivo and in vitro. In order to determine whether adrenal hormones might mediate the genotoxic effects of morphine, adrenalectomized and sham-operated mice were treated with morphine sulfate. In sham-operated animals administration of morphine produced a dose-related increase in the frequency of micronucleated cells, whereas adrenalectomy abolished the effect. When plasma from morphine-treated mice was used to supplement growth medium of untreated splenocytes, the frequency of micronucleated cells increased, an effect partially blocked by the steroid antagonist RU 486. The N-methylmorphine, which does not stimulate the release of corticosterone from adrenal glands, induced micronuclei formation in splenocytes, and administration of metyrapone, an inhibitor of corticosterone biosynthesis, blocked the morphine-induced increase in corticosterone secretion, but had no effect on the frequency of micronuclei formation. These results indicate that basal levels of glucocorticosteroids are required for induction of micronuclei by morphine in murine splenocytes, but activation of the hypothalamo–pituitary–adrenal (HPA) axis by morphine does not contribute to the observed response.

Plasma Corticosterone in Nestling American Kestrels: Effects of Age, Handling Stress, Yolk Androgens, and Body Condition

The effects of age, handling-induced stress, yolk androgens, and body condition on plasma corticosterone levels were investigated in free-living nestling American kestrels, Falco sparverius, a semialtricial falcon species. In an observational study, corticosterone levels varied with age and handling time. Specifically, corticosterone was low until age 15 days and then rose from age 20 through 25 days. Nestlings as young as age 10 days showed a handling-induced rise in corticosterone. Neither sex nor hatching order of the nestling affected corticosterone levels. Concentrations of maternally derived yolk androgens have previously been shown to be lower in first-laid than in later-laid eggs in the clutch. In an experimental study, androgens were injected into the yolk of the first-laid egg to elevate its levels to those of later-laid eggs, a treatment that substantially reduces nestling body condition compared with that of controls. Yolk androgen treatment elevated posthatching corticosterone levels compared with those of controls, and corticosterone levels were negatively correlated with body condition. These findings indicate that even very young, developing birds can show stress-induced increases in corticosterone and that age-related changes in corticosterone secretion may be modified by body condition and maternal effects such as yolk androgen deposition. The short- and long-term consequences of high glucocorticosteroid levels in young, developing vertebrates are largely unknown.

Seasonal changes in plasma testosterone and glucocorticosteroids in free-living male yellow-pine chipmunks and the response to capture and handling.

We measured plasma levels of testosterone, corticosterone, and cortisol in free-living male yellow-pine chipmunks to demonstrate the patterns of seasonal variation and to assess the effects of capture and handling on hormone levels. We achieved the latter by modifying our standard trapping technique (blood samples collected within 1-3 h of capture) to obtain blood samples that allowed measurement of hormone levels within 3 min of capture (basal) and again 30 min later. By alternating the modified and standard trapping techniques over 7 months of the active season we demonstrated that seasonal patterns of variation in steroid hormone levels can be accurately described with the simpler, standard trapping technique. Basal and 30-min post-capture testosterone levels were high during mating and dropped to a persistently low level thereafter. Conversely, both cortisol and corticosterone were at their seasonal low during mating and climbed to peak levels in June following reproduction. Plasma glucocorticosteroid levels increased during the 30 min after capture and handling at all times of the active season, and these elevated levels were similar to the levels obtained by standard trapping. Testosterone levels during the mating period also increased in response to capture and handling. The contrasting patterns of seasonal variation in glucocorticosteroid and testosterone levels and the changes induced by capture and handling suggest that when testosterone concentration is high, adrenocortical activity is suppressed.

Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus).

Nontropical rodents often experience large seasonal fluctuations in both food availability and energy demands. The energy required for thermoregulation is highest during the winter when food availability may be at an annual minimum. Failure to cope with winter probably accounts, in part, for the increased prevalence of disease and death relative to that in summer. Winter conditions may elevate circulating glucocorticosteroid levels, which can compromise immune function. To increase the odds of surviving the energetic demands of winter, individuals of some rodent species appear to enhance immune function before conditions deteriorate. Previous laboratory studies suggest that immune enhancement can be induced by short days. These findings contrast with the results of several field studies reporting suppressed immune function during the winter. To resolve this conflict, the authors hypothesized that winter stressors present in field studies counteracted the short-day enhancement of immune function reported in laboratory studies. If true, then immune function of captive mice in short days should be compromised by low temperature or reduced food availability. Both ambient temperature and photoperiod were manipulated in the present study to assess their effects on immune parameters in male deer mice (Peromyscus maniculatus). Animals in short days regressed their reproductive systems and also displayed significantly higher immunoglobulin G (IgG) levels than did those in long days. Deer mice maintained in low temperatures had significantly reduced splenic masses and basal IgG levels independent of day length. Animals maintained in both short days and low temperatures displayed IgG levels comparable to those of mice in long-day/mild-temperature conditions. Animals maintained in long days and low temperatures had significantly higher serum corticosterone levels than did animals maintained in long days at mild temperatures. These data are consistent with the hypothesis that immune parameters are enhanced in short days to counteract stress-mediated immune suppression occurring during the winter.

Lung epithelial Na channel subunits are differentially regulated during development and by steroids

Because the alpha-subunit of the rat lung epithelial Na channel (rENaC) is not expressed until late fetal gestation, the developmental immaturity of alpha-rENaC may be involved in the premature fetal lung's inability to mount a Na-absorptive response to appropriate agonists. As previous work has shown that the beta- and gamma-rENaC subunits of the Na channel are required for maximal alpha-rENaC activity, we determined their developmental expression in the fetal lung. In addition, because thyroid and corticosteroid therapy can mature the in vivo fetal lamb lung's ability to transport Na, we wished to determine whether such treatment increased the expression of alpha-, beta-, and gamma-rENaC. Lungs were harvested from normal rat fetuses of 17 through 22 days gestation (term = 22 days), normal rat pups during the first week of life, and adult rats. Initial expression of alpha-rENaC was detected at 19 days gestation and progressively increased in utero. beta- and gamma-rENaC mRNA were not detected until 21 and 22 days gestation, and then only at very low levels. During the first week after birth, the levels of alpha-rENaC declined, whereas beta- and gamma-rENaC mRNA levels increased. This pre- and postnatal pattern of alpha-rENaC expression correlates with the endogenous glucocorticosteroid levels in the fetus and the rat pup's early postnatal corticosteroid resistance. Combined or separate treatment of pregnant rats (16 through 22 days gestational age) with thyroid-releasing hormone (TRH) and/or dexamethasone (Dex) for 48 h showed that Dex, but not TRH, could increase fetal lung alpha-rENaC mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid and efficient method for extraction and separation of glucocorticosteroids and sex steroids from urines

The influence of different pH values on the recoveries of glucocorticosteroids and sex steroids from Kieselguhrfilled minicolumns has been investigated. While the recoveries of all steroids tested were similar if samples had acidic or neutral pH values, sex steroids could effectively be separated from glucocorticosteroids by increasing the pH value of 13.7: recoveries were 1.7% for glucocorticosteroids and 56–76% for sex steroids. For the determination of sex steroids in biological samples it is recommended to adjust samples to a strong alkaline pH before extraction; this holds especially true for samples with very high glucocorticosteroid levels.

Regulatory effects of aerosolized budesonide and adrenalectomy on the lung content of endothelin-1 in the rat.

This study was designed to investigate the effect of inflammation and glucocorticosteroids (GCS) on the content of endothelin-1-like immunoreactivity (ET-LI) in the rat lung. Following intratracheal instillation of Sephadex beads, which induces a long-lasting inflammation in the lung, there was an increase in the lung content of ET-LI measured by RIA. This increase was abolished by locally administered aerosolized budesonide at doses that had only minor systemic effects (measured as a reduction in body weight). In a second series of experiments, rats were subjected to surgical adrenalectomy in order to reduce the levels of endogenous GCS. This procedure elevated the ET-LI levels in the lungs. In contrast, neither adrenalectomy nor high doses of budesonide administered systemically affected the concentration of ET-LI in the kidney. It is concluded that the lung ET levels are elevated in inflammatory conditions and that this increase is highly sensitive to locally administered GCS. Endogenous GCS may, directly or indirectly, play a role in the regulation of lung ET content but there seems to be no general GCS effect on basal tissue levels of ET.

Hormonal and behavioural responses to simulated territorial intrusion in the cooperatively breeding white-browed sparrow weaver, Plocepasser mahali

Abstract. Behavioural investigations of stable groups of white-browed sparrow weavers indicate that they not only bred cooperatively, but also defended territories from other groups. Territory defence involved regular patrolling of boundaries plus a characteristic chorus vocalization that was given by all group members in concert. Song was performed exclusively by the breeding male and only during the breeding season. Territorial choruses were given by all members of the group at all seasons and could also be initiated by all members, although the breeding male and female initiated more choruses than helpers. Simulated territorial intrusions (achieved by placing a caged group within a territory and playing back tape-recorded choruses through a speaker placed alongside) resulted in dramatic increases in territorial aggression by all group members. Plasma levels of testosterone were not affected by the intrusions in breeding birds or helpers. However, plasma levels of luteinizing hormone were significantly elevated in the breeding females after challenge. These data are consistent with other observations in this species that territorial aggression is independent of circulating testosterone, but is correlated with luteinizing hormone. Corticosterone levels were higher in controls than in birds exposed to simulated territorial intrusions with the exception of breeding females. Although the significance of this latter result is unclear, it does seem likely that 'psychological castration' of non-breeders is not mediated through elevated circulating levels of glucocorticosteroids.

Interleukin-1-induced nonspecific resistance to bacterial infection in mice is not mediated by glucocorticosteroids.

Preexposure to a low dose of interleukin-1 (IL-1; 3 to 30 micrograms/kg) 24 h before a lethal gram-negative bacterial infection prolonged survival in normal and granulocytopenic mice. To examine whether this protective effect is mediated by glucocorticosteroids, we first measured corticosterone concentrations in mice after administration of 80 and 800 ng of IL-1. IL-1 induced a dose-dependent increase in corticosterone levels in plasma. Next, the corticosterone peak induced by a protective dose of IL-1 (800 ng) was simulated by administration of synthetic human adrenocorticotropic hormone 1-24 (ACTH) in normal and neutropenic mice. Although corticosterone levels induced by pretreatment with IL-1 or ACTH were virtually identical, the ACTH-induced corticosterone peak was not associated with protection against Klebsiella pneumoniae infection in normal mice and Pseudomonas aeruginosa infection in neutropenic mice. This indicates that the protective effect of IL-1 pretreatment against gram-negative bacterial infection is not mediated by elevated levels of glucocorticosteroids. In addition, we found that plasma corticosterone concentrations during K. pneumoniae infection were significantly lower after pretreatment with IL-1 than after pretreatment with ACTH or vehicle, probably reflecting the better physical condition of IL-1-treated mice.

Comparison of the Adrenocortical Responseto both Pharmacological and Physiological Stressesin Sport Horses

Seven sport horses were investigated to compare physiological and pharmacological stresses on the plasma glucocorticosteroid levels. Venous blood was sampled and analysed for cortisol concentrations before and after each type of stress. The physiological stress was induced by the completion of a cross-country and the pharmacological one, by an intravenous ACTH administration (200 micrograms) in the same horses, one week after the course. Both exercise and ACTH injection induced a highly significant cortisol increase of 79 +/- 0.10% and 160 +/- 0.18%, respectively. The relative plasma cortisol increases due to exercise on the one hand, and due to ACTH administration on the other hand, were correlated with a coefficient of 0.82. It was concluded that the plasma cortisol increase induced by a standardised pharmacological stress could be used in order to predict the exercise-induced stress response.

Immunotoxicity studies of PCB (Aroclor 1254) in the adult rhesus ( Macaca Mulatta) monkey — preliminary report

The effects of PCB (Aroclor 1254) on the immune system of adult female rhesus monkeys were investigated in a chronic study wherein five groups of monkeys (16/group) were administered (orally) PCB at levels of 0.0, 5.0, 20.0, 40.0 or 80.0 μg/kg body wt daily. Tests for immunotoxicity were initiated at 23 months of exposure to PCB, at which time the monkeys had achieved an apparent pharmacokinetic steady state based on the PCB concentration in fat and/or blood. A statistically significant ( P<0.05) dose response reduction in antibody levels (IgG and IgM) to sheep red blood cells (SRBC) was observed following i.v. administration of three immunizing doses of SRBC at weekly intervals. A statistically significant decrease in the percent T H and an increase in the percent and absolute T S lymphocyte levels was found in the 80 μg/kg body wt group compared to the control. The T H/ T S ratio was also significantly lower in the 80 μg/kg body wt group compared to the control. Other parameters investigated including percent of B-lymphocytes and total T-lymphocytes, total serum immunoglobulin levels (IgG, IgM and IgA), other serum proteins, glucocorticosteroid levels and lymphocyte transformation results following stimulation with the mitogens PHA-P and Con A were not affected significantly by PCB treatment. Additional immunologic parameters are currently being investigated to further elucidate the mechanism by which PCB induces immunotoxicity.

Studies on the mechanism of action of the inhibitory effect of the somatostatin analog SMS 201-995 on the growth of the prolactin/adrenocorticotropin-secreting pituitary tumor 7315a.

The somatostatin analog SMS 201-995 (2 X 6 or 2 X 20 micrograms daily for 30 days) inhibited the growth of the PRL/ACTH-secreting pituitary tumor 7315a by 36% and 48%, respectively. A biphasic curve of the inhibitory effect of the SMS analog on tumor growth was recognized: the actual tumor growth inhibitory effect occurred during the first 15 days, after which the tumors grew in parallel with the control tumors despite SMS 201-995 treatment. At the end of the 30-day SMS 201-995 treatment, plasma GH and plasma somatomedin-C levels were similar to those in the control tumor-bearing rats. Separate experiments in normal rats showed that tachyphylaxis of the GH-secretion inhibitory effects of three different doses of SMS 201-995 occurred within 6-10 days. No specific somatostatin-14 or SMS 201-995 receptors were present on well grown, untreated 7315a pituitary tumors. However, PRL and ACTH secretion by cultured cells prepared from the 7315a tumor was inhibited by SMS 201-995. Pretreatment of the cultured cells with dexamethasone made PRL secretion by these tumor cells insensitive to SMS 201-995. These studies suggest that several factors played a role in the mechanism of action of the tumor growth-inhibitory actions of SMS 201-995. Twice daily administration of the somatostatin analog rapidly (within 6-10 days) induces tachyphylaxis of the GH-inhibitory effect. From 10 days after implantation the PRL/ACTH-secreting pituitary tumor causes adrenal hyperplasia and increased plasma corticosterone concentrations. Exposure of the 7315a tumor to high glucocorticosteroid levels probably decreases the number of somatostatin receptors, diminishing the possible direct antitumor effect of SMS 201-995.

Developmental and hormonal regulation of carbamoyl-phosphate synthase gene expression in rat liver: Evidence for control mechanisms at different levels in the perinatal period

Carbamoyl-phosphate synthase gene expression is found to be primarily regulated by conditions that enhance hepatic glucocorticosteroid levels (hormone injections) and cyclic AMP levels (induction of diabetes). After birth, changes in the level of carbamoyl-phosphate synthase protein follow changes in the level of carbamoyl-phosphate synthase mRNA, suggesting a pretranslational control mechanism. In fetal rats, carbamoyl-phosphate synthase gene expression is regulated by the same factors as in adults. However, both the level to which carbamoyl-phosphate synthase mRNA can accumulate and the extent to which mRNA can be translated appear to be limited, indicating control mechanisms at the pretranslational and translational level. Finally, in the immediate postnatal period, a transient but pronounced decrease in the rate of degradation of carbamoyl-phosphate synthase protein may play a role in the accumulation of the enzyme.