Blood Corticosteroid Levels Research Articles

Comparative study on molecular mechanism of diabetic myopathy in two different types of streptozotocin-induced diabetic models

AimsStreptozotocin (STZ)-induced diabetic animal models have been widely used to study diabetic myopathy; however, non-specific cytotoxic effects of high-dose STZ have been discussed. The purpose of this study was to compare diabetic myopathy in a high-STZ model with another well-established STZ model with reduced cytotoxicity (high-fat diet (HFD) and low-dose STZ) and to identify mechanistic insights underlying diabetic myopathy in STZ models that can mimic perturbations observed in human patients with diabetic myopathy. Main methodsMale C57BL6 mice were injected with a single high dose of STZ (180 mg/kg, High-STZ) or were given HFD plus low-dose STZ injection (STZ, 55 mg/kg/day, five consecutive days, HFD/STZ). We characterized diabetic myopathy by histological and immunochemical analyses and conducted gene expression analysis. Key findingsThe high-STZ model showed a significant reduction in tibialis anterior myofiber size along with decreased satellite cell content and downregulation of inflammation response and collagen gene expression. Interestingly, blood corticosteroid levels were significantly increased in the high-STZ model, which was possibly related to lowered inflammation response-related gene expression. Further analyses using the HFD/STZ model showed downregulation of gene expression related to mitochondrial functions accompanied by a significant decrease in ATP levels in the muscles. SignificanceThe high-STZ model is suitable for studies regarding not only severe diabetic myopathy with excessive blood glucose but also negative impact of glucocorticoids on skeletal muscles. In contrast, the HFD/STZ model is characterized by higher immune responses and lower ATP production, which also reflects the pathologies observed in human diabetic patients.

New reagents for poultry research: preparation, purification, and in vitro evaluation of non-PEGylated and mono-PEGylated chicken prolactin

Recombinant chicken prolactin (chPRL), expressed in Escherichia coli and purified as a monomer, was successfully PEGylated and purified to homogeneity as a mono-PEGylated protein (PEG-chPRL). Its biological activity was estimated by its ability to interact with human prolactin receptor extracellular domain (hPRLR-ECD) and stimulate PRLR-mediated proliferation in Nb2-11C cells. PEG-chPRL activity in a cell bioassay was 10-fold lower than that of non-PEGylated chPRL, but only 2-fold lower in a binding assay to hPRLR-ECD. The CD spectra of non-PEGylated and PEGylated chPRL were almost identical and similar to that of hPRL, indicating proper refolding. Although the PEGylation of chPRL resulted in lower activity in vitro, PEG-chPRL was absorbed more slowly than chPRL, remained in the circulation 16h longer. Furthermore the effects of PEG-chPRL injections in chickens on subsequent corticosteroid levels in blood were significantly profound compared to chPRL. These favorable PEGylation-induced pharmacokinetic alterations should improve efficacy of PEG-chPRL in in vivo experiments, as dosing frequency can be reduced due to its prolonged persistence in the circulation, and thus reduce the frequency of dosing. Furthermore, hydrophobic interaction chromatography was successfully adopted to isolate PEG-chPRL as a better alternative for separation of PEGylated PRL, and is likely to be successfully applicable to other proteins.

Hypothalamic-pituitary-adrenal system and enzymes of the glutathione-dependent antioxidant system during stress and aging

Activity of glutathione-dependent antioxidant enzymes (glutathione peroxidase, glutathione reductase, and glutathione transferase) in blood erythrocytes from female Macaca mulatta (6-8 and 20-26 years) was measured during activation of the hypothalamic-pituitary-adrenal system under conditions of acute psychoemotional stress (2-h restraint stress). Glutathione reductase activity increased during stress, depended on the time of day, and strongly correlated with blood corticosteroid level. Circadian variations in stress reactivity of glutathione reductase during aging were accompanied by similar changes in stress reactivity of the hypothalamic-pituitary-adrenal system.

Do Corticosteroids Damage the Brain?

Corticosteroids are an essential component of the body's homeostatic system. In common with other such systems, this implies that corticosteroid levels in blood and, more importantly, in the tissues remain within an optimal range. It also implies that this range may vary according to circumstance. Lack of corticosteroids, such as untreated Addison's disease, can be fatal in humans. In this review, we are principally concerned with excess or disturbed patterns of circulating corticosteroids in the longer or shorter term, and the effects they have on the brain.

Specific GABA binding in the adrenals and blood corticosteroid levels in stress in intact rats and rats with changes in the functional activity of the hypothalamo-pituitary-adrenal system.

Thirty minutes of swimming led to decreases in the specific binding of GABA to adrenal plasma membranes in intact rats, but not in rats repeatedly given hydrocortisone to inhibit the baseline activity of the hypothalamic-pituitary-adrenal cortex system, where the level of reception of this amino acid was significantly greater than in controls. Pre-stress administration of baclofen and gamma-L-aminobutyryltaurine had no effect on specific GABA binding, even though these agents affected blood corticosterone concentrations.

Specific GABA binding in the adrenals and blood corticosteroid level in stress in intact rats and rats with changed functional activity of the hypothalamo-pituitary-adrenal system

Thirty-minutes swimming of rats led to a decrease of specific GABA binding by adrenal plasmatic membranes in intact rats but not in rats with increased level of amino acid reception repeatedly injected with hydrocortisone for inhibition of basal hypothalamic-pituitary-adrenal activity. In jections of baclophene and gamma-L-aminobutyril-taurine before stress did not modify the specific GABA binding, although the drugs changed the corticosteroid concentrations in the blood.

Role of Corticosteroids In Cadmium Induced Immunotoxicity

ABSTRACTCadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p<0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Amino glutethemide when administered alone caused significant (p<0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.

Stress-induced analgesia. The role of hormones produced by the hypophyseal-adrenocortical system.

Experimental studies on the effects of stress on blood corticosteroid levels and the appearance of analgesia were carried out on rats anesthetized with Nembutai (4 mg/100 g). Stress, consisting of stimulation of the hind footpad with a current at 0.7 mA, produced parallel changes in plasma corticosteroid concentrations and the threshold of a pain response. Functional blockade of the hypophyseal-adrenocortical system, produced by systemic administration of hydrocortisone (15 mg/100 g) or by implantation of dexamethasone (200 micrograms) above the paraventricular nucleus of the hypothalamus, resulted in reductions in stress-induced analgesia. Dosage with naloxone (1 and 10 mg/kg) had no effect on the level of analgesia or corticosteroid concentrations. It is concluded that stress-induced analgesia not mediated by opioids is corticosteroid-dependent.

Patterns of interaction between the immune and endocrine systems in the manifestation of hereditary autoimmune disorders in NZB mice

Specific features of immune-endocrine interrelationships and of pituitary-adrenal system functioning are studied in NZB mice with hereditary autoimmune pathology. It is established that the development of disease is accompanied by a weakened response to stress, reduced blood corticosteroid level, and decreased adrenal reactivity to exogenous adrenocorticotropic hormone. Moreover, a loss of sensitivity to interleukin-2 is observed. These facts provide evidence of disturbed interaction between the immune and endocrine systems as well as of inhibition of pituitary-adrenal system activity as the autoimmune disease develops.

Liver microsomal cytochrome: P-450p and P-450h activity and blood corticosteroid levels of experimental animals exposed to physical factors

Liver microsomal cytochrome: P-450p and P-450h activity and blood corticosteroid levels of experimental animals exposed to physical factors

Endogenous Corticosteroids Mediate Seasonal Cyclic Changes in Immunity of Lizards

Endogenous corticosteroid (CS) blood levels were radioimmunoassayed in fresh, field-collected lizards Chalcides ocellatus at two week-intervals throughout the four consecutive seasons. These animals were used in parallel to investigate the splenic T and B lymphocyte level, lymphoprolif erative responsiveness to concanavalin A and primary antibody production in vitro against rat erythrocytes (RRBC). The recorded data indicated that fully developed splenic lymphoid tissue and powerful immune responsiveness are coincident with a continuously low CS level, and characterize the period from spring through early autumn. On the other hand, the dramatic lymphocytic destruction and impairment of immune reactivity observed in autumn and winter are associated with not only a high, but above all sustained, rise in endogenous CS levels. Apparently, exposure of lizard lymphocytes to comparatively high, yet physiologic, levels of endogenous CS for prolonged periods of time lead to impairment of their immune functions. In support, long-term administration of exogenous hydrocortisone acetate (HC) to ,summer- lizards resulted in a high and lasting elevation in blood CS levels that was associated with a considerable depletion of lymphoid elements and abrogation of immune reactivity, exactly as in normal lizards collected from the field in autumn through winter. In addition, pharmacologic inhibition of CS synthesis by administration of metyrapone at the beginning of autumn greatly modulated the lizard lymphocyte response to the autumn-related immunodepression. The study thus strongly suggests that the autumn/winter-dependent immunosuppression in lizards is essentially due to a high and lasting rise in levels of endogenous CS. The results are discussed from the perspective of the role played by CS in mediating the seasonal rhythms that affect reptilian immunity.

Corticosteroid levels in human fetal blood at midgestation and at term

Cortisol and cortisone were estimated in samples of fetal blood obtained by fetoscopy at 13 to 24 weeks' gestation and in cord blood obtained at elective cesarean section at 38 weeks' gestation. Levels of cortisone exceeded those of cortisol at all gestational ages studied. At midgestation, cortisol levels tended to fall with advancing gestation and had a weak negative correlation with fetal weight. The levels of both steroids were similar in male and female fetuses and increased significantly from midgestation to tem.

Role of the paraventricular and ventromedial hypothalamic nuclear areas in the regulation of the pituitary - adrenocortical system

The role of the paraventricular (PVN) and ventromedial (VMN) hypothalamic nuclei in the activation and inhibition of the pituitary-adrenocortical system was studied in chronic experiments on rabbits. The functioning of the pituitary-adrenocortical system was estimated by changes in blood corticosteroid levels. PVN and VMN lesions resulted in a reduction of the stress-induced corticosteroid rise. VMN lesions resulted in smaller changes of the stress-induced response than PVN lesions while combined VMN and PVN lesions did not cause a larger reduction of the stress-induced activation than lesions of either area. The data obtained confirm that the PVN and VMN are connected in series. Hydrocortisone (100 μg/kg) administered intravenoously 5 min before immobilization inhibits the stress-induced corticosteroid rise in intacts rabbits. PVN and VMN lesions result in a reduction of the hydrocortisone inhibitory effect, PVN lesions having a greater effect than VMN ones. The PVN is of greater importance in both the activation and the inhibition of the pituitary-adrenocortical system than the VMN.

Vasopressin, ACTH, and blood pressure during hypoxia induced at different rates.

We decreased arterial PO2 at three different rates and measured blood pressure (BP), vasopressin (AVP), ACTH, and corticosteroid levels in nonsurgically stressed, anesthetized, paralyzed dogs. PaO2 was lowered to 28 Torr in 2 (fast), 10 (moderate), and 20 min (slow). The fast dPO2/dt produced a large spike in BP. Increases in AVP, ACTH, and corticosteroids were similar regardless of the dPO2/dt. When the spike in BP during the fast dPO2/dt was prevented with nitroprusside, hormone levels increased more quickly and were higher during the first 20-30 min of hypoxia. By 60 min, hormone levels were not different between experiments. The data suggest that 1) faster decreases in PO2 produce larger increases in BP, 2) increases in AVP, ACTH, and corticosteroids are primarily sensitive to the level of steady-state PaO2, and 3) increases in BP inhibit stress-induced increases in AVP and ACTH.

Genetic and environmental aspects of the immune response

The main characteristic of the immune system is the potency to detect and resist invasions of foreign substances such as viruses, bacteria, parasites and transformed malignant cells. This ability is characterized and determined mostly by macrophage activity and T and B lymphocytes. These three major components of the immune response are independently genetically regulated. This makes selection on the basis of the immune response difficult. Environmental factors can induce stress situations which result in high blood corticosteroid levels. Corticosteroids can be immunosuppressive. In modern animal husbandry practice such factors exist and can influence disease resistance resulting in multifactorial diseases.

Genetic and environmental aspects of the immune response

Abstract The main characteristic of the immune system is the potency to detect and resist invasions of foreign substances such as viruses, bacteria, parasites and transformed malignant cells. This ability is characterized and determined mostly by macrophage activity and T and B lymphocytes. These three major components of the immune response are independently genetically regulated. This makes selection on the basis of the immune response difficult. Environmental factors can induce stress situations which result in high blood corticosteroid levels. Corticosteroids can be immunosuppressive. In modern animal husbandry practice such factors exist and can influence disease resistance resulting in multifactorial diseases.

Role of the medial hypothalamus in regulation of the pituitary-adrenocortical system

Chronic experiments on rabbits showed that bilateral electrolytic destruction of dorosomedial and ventromedial hypothalamic nuclei lowers the basal blood corticosteroid levels. Stimulation of the dorsal tegmentum, which in intact animals causes the blood corticosteroids to rise, no longer leads to an increase in the adrenocortical hormone level after destruction of these nuclei. It is concluded that the medial hypothalamus has a tonic activating influence on basal secretion and participates in transmission of activating influences from the midbrain to the adrenal cortex.

Inhibition of corticosteroid production by pineal factor

The effect of a factor isolated from the bovine pineal gland on the blood corticosteroid level and on the ability of isolated adrenal tissue to synthesize these compounds was investigated in experiments on male Wistar rats. The method of obtaining the pineal fraction is described. Its injection in a dose of 2 mg/100 g body weight lowered the blood corticosteroid level by 74, 69, 40, 64, and 63% after 4, 5, 7, 9, and 12 days respectively. The ability of the adrenal tissue to synthesize corticosteroids was depressed. The results are evidence that the pineal gland participates in the regulation of adrenal function.

The effects of ACTH on adrenal steroidogenesis and blood corticosteroid levels in the echidna ( Tachyglossus aculeatus)

1. 1. The effects of short-term (S.T., 30 min) and long-term (L.T., 4 days) administration of ACTH on peripheral blood corticosteroid levels and on in vitro steroidogenesis were investigated. 2. 2. Control levels of cortisol, corticosterone and aldosterone were 58 ± 12, 130 ± 26 and 10 ± 6 (SEM) ng/100 ml respectively. 3. 3. Corticosterone was 70% higher after S.T. and 150% higher after L.T., when cortisol was 800% higher. 4. 4. Adrenal homogenates from control echidnas converted [ 14C]progesterone predominantly to 11-deoxycorticosterone (45%) and 11-deoxycortisol (12%). 5. 5. After L.T. the principal product was corticosterone (25%), but S.T. had no effect. 6. 6. In control echidnas the K m , and V for 11β-hydroxylation of 11-deoxycorticosterone were 20 μM and 2.8 ρmol/min/mg respectively. After L.T. V increased to 10 ρmol/min/mg.

Electrical activity of hypothalamus during activation of pituitary-adrenocortical system

Multiunit activity in anterior (AHA), medial (MHA) and lateral (LHA) areas of hypothalamus during activation of the pituitary-adrenocortical system was measured in chronic experiments on rabbits. Immobilization causing blood-corticosteroid levels to rise was followed by the excitation of most pools of neurons in MHA, and by inhibition in AHA and LHA. When immobilization failed to induce stimulation of MHA (as a result of pretreatment with large doses of cortisol), it did not cause blood-corticosteroid levels to rise, either, The switching off activity in AHA and MHA is considered to be a manifestation of functional changes which are responsible for stress-induced activation of the adrenocortical system.