Adrenal function of rats in hypokinesia

Histological and biochemical examinations of the adrenals and plasma of rats for 3 months exposed to hypokinesia have shown that low motor activity led to a decrease in blood corticosterone level in spite of adrenal cortex hypertrophy. The decreased corticosterone blood level was not indicative of adrenal exhaustion, as the adrenals produced a greater amount of corticosterone in response to additional stress stimulus (5-hour immobilisation of animals in an extended state), as compared to the control. The increased production of corticosterone in response to stress stimulus caused no structural transformations or delipoidization of the cortical substance. This indicated that the reserve potentials of the adrenals increased with the animal adaptation to hypokinesia. The major morphological indication of higher adrenal functional activity in hypokinetic animals was an enhanced destruction of lymphocytes in the thymus cortex, the target organ for corticosteroids produced by the adrenals in response to an additional stress stimulus.     

Genetic determination of the response of the mouse hypothalamo-hypophyseo-adrenal system to cold and immobilization stress]

Peculiarities of the hypothalamo-pituitary-adrenal system (HPAS) reaction in mice of 8 inbred strains to a stress effect of the immoblization and of cold have been studied and a comparison of the effect with the reaction of the adrenal cortex to its direct stimulator--ACTH have been carried out. As a result of the study of the resting level of 11-hydroxycorticosteroids in peripheral plasma of inbred mice significant interstrain differences were found. A positive correlation between resting corticosteroids level and the reaction of HPAS to the stress in mouse strains under study was found, but none of them correlated with the reactivity of the adrenal cortex to ACTH.     

Circadian and age-related changes in stress responsiveness of the adrenal cortex and erythrocyte antioxidant enzymes in female rhesus monkeys

Background The objective of this study was to evaluate the role of the adrenal cortex in the regulation of antioxidant enzyme defense and to characterize this regulation in different age periods. Methods Five young and five old female rhesus monkeys were subjected to 2 hours squeeze cage restraint stress at 0900 or 1500 hours. Plasma levels of corticosteroids and activities of erythrocyte antioxidant enzymes were measured before the stress and 30, 60, 120, 240 minutes after beginning of the stress. Results Young monkeys showed a circadian rhythm in stress responsiveness as measured by corticosteroids and glutathione reductase. The rhythm was attenuated in old animals. Age‐related changes in the overall level of response to the afternoon stress were also seen in the corticosteroid and glutathione reductase measures. Conclusions The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age.     

Functional morphology of the adrenal cortex during the physiological rhythm of sex steroid synthesis]

A method of a quantitative histenzymological analysis was used for determination of the extent of participation of various zones of the adrenal cortex in provision of physiological rhythm of the steroid synthesis. The activity of 3beta-OH-steroid dehydrogenase, glucoso-6-phosphat dehydrogenase, NAD- and NADP-diaphorases, acid and alkaline phosphatases and non-specific esterase was investigated. The data of a histoenzymotological study were compared with the result of biochemical analysis of corticosteroids in the peripheral blood. Under physiological conditions intensification of steroidogenesis was realized by mobilization of individual groups of cells of the adrenal gland, not its whole parenchyma. Physiological rhythm of steroid synthesis was provided by an integrated function of all the zones; however, by duration and quantitative expression of the secretory activity a structural heterogeneity was revealed in the adrenal cortex.     

Cucurbitacin R glycoside--a regulator of steroidogenesis and of the formation of prostaglandin E2--a specific modulator of the hypothalamus-hypophysis-adrenal cortex system

2 beta,25-di(0-beta-D-glucopyranosyloxy)-16 alpha,20-dihydroxycucurbit-5-en-3,11,22-trione (cucurbitacin R glucoside--CRG), isolated from Bryonia alba roots, stimulates corticosterone secretion in the adrenal cortex of rats and augments the working capacity of mice. If rats after CRG injections were exposed to immobilization stress, the level of corticosterone in the adrenal cortex and blood plasma was not increased, like in the control groups of rats not receiving CRG. The level of prostaglandin E2 in the adrenal cortex was increased during stress and after CRG administration. These findings indicate that CRG regulates steroidogenesis by influencing the activity of prostaglandin G2-prostaglandin E2 isomerase.     

Electroencephalographic analysis of inter-central relations in hypothalamo-reticulo-limbic brain structures during treatment with corticosteroids and neuropeptides

Intercentral relations between hypothalamus, limbic system and reticular formation were studied in rabbits and rats under systemic and central action of DSIP, ACTH, corticosteroids and stress (aggressive-defensive behaviour). The results obtained demonstrate changes in the adrenal cortex resulting from stress-inducing adrenocortical hormone content. The increase was achieved by the rise in ACTH level resulting in corticosteroid level elevation (endogenous elevation-aggressive behaviour) and by corticosteroid injections (exogenous elevation). Correlation analysis of structural interrelations after ACTH and corticosteroid injections demonstrated an increased correlation between hypothalamo-reticular-limbic structures. DSIP was shown to have an opposite effect. Correlation analysis revealed the potentials for the formation of new functional interrelations between hypothalamo-reticular-limbic structure in the motivation of aggression (stress) and the levels of corticosterone and DSIP. DSIP action depends on the initial corticosteroid blood level and is more marked in stress-inducing concentrations.     

Quantitative evaluation of ultrastructural restructuring in the adrenal cortex of rats under stress

Quantitative and qualitative analysis has revealed that submicroscopic changes of the rat adrenal cortex in dynamics of the stress reaction examined at the level of "functional element" which combines basic structural components of the parenchyma and stroma are of the polyphase character and agree with data from the biochemical analysis of 11-OCS in blood plasma. At the stage of exhaustion of the stress reaction (72 hours of immobilization) the ultrastructure of the adrenal cortex testifies to the preservation of functional reserves in the secretory cells.     

Recurrent long-lasting tethering reduces BDNF protein levels in the dorsal hippocampus and frontal cortex in pigs

Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the onset of depression and in antidepressant efficacy, although the exact role of this neurotrophin in the pathophysiology of depression remains to be elucidated. Also, the interaction between chronic stress, which may precede depression, corticosteroids and BDNF is not fully understood. The present study aimed at investigating whether long-lasting, recurrent tethering of sows during a period of 1.5 or 4.5 years leads to enduring effects on measures that may be indicative of chronic stress, compared with animals kept in a group housing system ('loose' sows). Immediately after slaughter, the frontal cortex, dorsal and ventral hippocampus were dissected and protein levels of BDNF and its receptors were analyzed and compared with plasma cortisol levels and adrenal weights. Results indicate that tethering stress reduced BDNF protein levels in the dorsal hippocampus and the frontal cortex, but not in the ventral hippocampus. In addition, levels of TrkB, the high affinity receptor for BDNF, were increased in the dorsal hippocampus. Plasma cortisol levels and adrenal weight were increased after tethering. These stress effects on BDNF levels were more pronounced after 4.5 years of recurrent tethering and negatively correlated in particular in the frontal cortex with cortisol levels and adrenal weight. This suggests that the stress effect of tethered housing on neurotrophin levels may be mediated via cortisol. Taken together, these data indicate that recurrent tethering stress in sows over 4.5 years results in a loss of neurotrophic support by BDNF, mediated by an overactive neuroendocrine system.     

Hydrocortisone modification during intrauterine development of the activity of brain tyrosine hydroxylase in adult white rats

The activity of the key enzyme of catecholamine synthesis, tyrosine hydroxylase (TH), and the level of corticosteroids in blood were estimated in adult white rats in the normal state and after stress after their mothers were treated with hydrocortisone during pregnancy. The disturbance of the balance of corticosteroids during intrauterine development decreases the initial activity of TH in hypothalamus but increases it in the cortex of adult animals. Besides, after stress the increase in the level of corticosteroids in blood is less pronounced but the TH activation in hypothalamus is more distinct. Hence, the increase in the level of corticosteroids during intrauterine development induces long-term changes in the TH activity in brain which may be one of the causes of decrease in reactivity of adult animals after stress.     

Relationship between functional activity of the adrenal glands and gonads in monkeys during puberty]

Testicular and adrenal cortex endocrine functions were simultaneously tested in pubertal baboons (papio hamadryas) during one year. Concentrations of androgens (testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone), corticosteroids (cortisol, progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone) and aldosterone were determined in blood of the experimental monkeys by radioimmunoassay. It was shown that with increasing androgen (testosterone and dihydrotestosterone) levels in blood of the pubertal monkeys there was a significant decrease of corticosteroid concentration which was most pronounced in the monkeys with maximum increase of testosterone level. Described hormonal changes did not influence aldosterone concentration.     

Development of the hormonal reaction to stress in the ontogenesis of the baboon Papio hamadryas

The hormonal reaction of adrenal and gonadal glands of baboons at various ages was studied under 2 hr immobilization stress condition. Concentrations of cortisol, 11-deoxycortisol, 17-hydroxypregnenolone, dehydroepiandrosterone and testosterone were determined by radioimmunoassay in the monkey blood plasma at different times during the stress reaction. A more pronounced reaction of adrenal cortex was shown in 1 year old baboons. The peak of cortisol level in immature monkeys under stress conditions was registered much earlier than in adult monkeys.     

Effect of 17beta-estradiol on content of cyclic nucleotides and protein kinases A and C activity in human adrenal cortex

The influence of 17beta-estradiol on cAMP and cGMP levels, protein kinases A and C activityand corticosteroids secretion was investigated in postoperative human adrenal cortex tissue. cAMP accumulation in adrenocorticocytes increased uiider the influence of 17beta-estradiol. In vitro estradiol raised the activities of protein kinases A and C in membrane fraction of adrenal cortex tissue. Significant increasing of steroidogenesis was observed. These data support our conclusion that cAMP dependent siganling system is involved in activation of steroidogenesis by 17beta-estradiol.     

The fine structural morphology of adrenal cortices of normal and stressed squirrel monkeys

The fine structural morphology of the male squirrel monkey adrenal cortex has been examined. When compared to other laboratory animals, the squirrel monkey adrenal cortex secretes large amounts of cortisol and maintains extraordinarily high plasma cortisol levels for prolonged periods of time. The normal cortical cells have numerous mitochondria with either a tubulo-vesicular or lamellar internal membrane arrangement, a well-developed agranular endoplasmic reticulum which is arranged in juxtaposition to mitochondria and lipid droplets, several lysosomes, and numerous thin-walled blood vessels of large caliber, suggestive of a rich blood flow through the gland. These characteristics have heretofore been associated with hypersecretion. Their presence in the squirrel monkey cortex, known to have high secretory activity, lends credence to the correlation of hyperdevelopment of the agranular reticulum with increased rates of secretion of corticoids. During chair restraint, the plasma cortisol levels rise two to three fold. Adrenocortical cells thus stressed exhibit a depletion and disorientation of membranes both of the agranular endoplasmic reticulum and mitochondria and a loss of ribosomes, lysosomes and, to some degree, intracellular lipid. The animal appears to be responding maximally to the stress of chair restraint. These fine structural characteristics are interpreted as an example of an adrenal cortex in the process of becoming functionally exhausted, since these animals sometimes do not survive the stress of chair restraint.     

Biosynthesis of androgens by pheochromocytomas

Homogenates from four adrenal pheochromocytomas converted 4-14C-labeled pregnenolone, 17-hydroxyprogesterone, and dehydroepiandrosterone into androstenedione and testosterone. In addition to these androgens, labeled pregnane substrates were also transformed into corticosteroids, as previously reported, and this conversion occurred in even higher yield. The formation of labeled metabolites of either pathway was greater in homogenates from intraadrenal pheochromocytomas than in those derived from an extraadrenal tumor, but less than in preparations of hyperplastic adrenal cortex. Incubations of subcellular fractions isolated from an adrenal pheochromocytoma showed that the enzyme activities involved in androgen formation from the radioactive substrates studied were associated with the microsomes and required exogenous cofactors. In contrast to adrenocortical tissue, chromaffin cell preparations uniformly failed to convert substrate [4-14C] cholesterol into either androgens or corticosteroids. The data available demonstrate the presence in chromaffin tissue of all of the enzyme activities required for the biosynthesis of androgens and corticosteroids except for those involved in the side-chain scission of cholesterol.     

The effect of biofeedback-assisted relaxation training on blood pressure and selected biochemical parameters in patients with essential hypertension

The effect of EMG biofeedback-assisted relaxation on blood pressure and selected biochemical parameters was evaluated in 38 patients with essential hypertension. Training consisted of 8 weeks of biofeedback and home practice of relaxation exercises. Mean blood pressure decreased in the experimental group from 144/90 to 133/84 mm Hg while the control group remained unchanged. Statistically significant decreases in the experimental group also occurred in muscle tension levels, in plasma aldosterone, and in urinary cortisol. Both aldosterone and cortisol are secreted by the adrenal cortex. It was concluded that the technique taught to the experimental group produced a reduction in skeletal muscle tension and a decrease in stress responding mediated by the adrenal cortex.     

18-Hydroxy-11-deoxycorticosterone in hypertensive uremic patients during hemodialysis.

The present study was carried out in 25 hypertensive uremic patients on regular 4 h dialysis, 3 times a week. Plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), aldosterone (PA) and corticosteroids were determined by radioimmunoassay and competitive protein binding technique before and at the end of the 1st, 2nd and 3rd hour of hemodialysis. Plasma 18-HD-DOC was normal before dialysis and did not change significantly during hemodialysis, whereas body fluids and electolytes decreased progressively. No correlation was observed between blood pressure and 18-OH-DOC during dialysis. 18-OH-DOC did not correlate with PA which decreases progressively during hemodialysis and was correlated to plasma corticosteroids only at the 3rd hour of dialysis, probably on account of the enhanced influence of ACTH on the adrenal cortex.     

The adrenocortical function of alloxan-induced diabetic rats

The purpose of this study is to investigate the adrenocortical function of alloxan-induced diabetic rats. Male rats of Wistar strain, weighing 200-250 gm were used. The results indicated that the adrenocortical response to stress and exogenous corticotropin (ACTH1-24) is decreased during the early diabetic stages (up to 6 days). Evidence from in vivo and in vitro studies shows that the depression is caused by the toxicity of alloxan on the adrenal cortex cells and not by the sudden rise of blood glucose levels. Streptozotocin (another diabetogen) has the same effect as alloxan on adrenal cortex cells.     

Effect of alpha-tocopherol on adrenal cortex functions under stress]

alpha-Tocopherol has been studied for its effect on lipid peroxidation and steroidogenesis in the adrenal cortices of rat and rabbit under stress. The vitamin is shown to exert an inhibitory effect on the lipid peroxidation developing under chronic stress. A biphasic pattern of the alpha-tocopherol effect on the steroidogenesis in the adrenal cortex is established: a decrease in the release of the steroids under the acute stress and maintaining of their levels under the chronic stress. A conclusion is drawn about a potential alpha-tocopherol application to correct the adrenal cortex function under stress.     

Morphofunctional characteristics of adrenal reactivity in rats of different ages

Ultrastructural peculiarities of the cortical and medullary substance of the adrenals have been studied in mature (8-month-old) and old (26-month-old) intact white male rats and in rats of the same age groups in 3 h after electrical stimulation of the hypothalamic ventromedial nuclei. By means of certain biochemical methods contents of hormones (corticosterone, adrenaline and noradrenaline) have been estimated, as well as that of cholesterin and ascorbic acid in blood and adrenal tissues. After the hypothalamus is stimulated in the mature rats, certain peculiarities in the adrenals reactivity are revealed; they demonstrate positive ultrastructural and functional correlation of secretory cells in the cortex and medulla and are characterized with hypertrophy of the nuclei, increased amount of polyribosomes, hypertrophied Golgi complex and canaliculi of the endoplasmic reticulum and increased contents of corticosteroids and catecholamines in blood. In the old rats after stimulation of the hypothalamus, certain unequal ultrastructural and functional peculiarities are revealed. They demonstrate both disturbance of the hypothalamic regulation of the adrenal function at ageing and decreased adaptive possibilities of the adrenal secretory cells at the subcellular level.     

Dynamic measure of production rate of cortisol in the mature guinea-pig in response to the stress of anesthesia: Effect of estradiol

The effect of estradiol on adrenal secretion rate of cortisol in response to a stress induced by anesthesia, was examined by comparing the metabolic clearance rate and the production rate of cortisol between males and females and after estradiol administration in castrated animals. Metabolic clearance rates of cortisol (MCR) were significantly higher (+30%) in males than in females. Castration lowered the MCR of cortisol in males and had no significant effect in females. After estradiol administration, a fall in the MCR of cortisol concomitant with a rise in blood cortisol level was observed especially in males in which the effect of treatment was more marked than in females and highly significant. The production rate of cortisol was identical in males and females and was slightly increased in estradiol-treated males and females. The data indicate that estradiol had an inhibitory effect on metabolic clearance of cortisol, which caused an important rise of blood cortisol levels in response to stress and which prevented an increase in the adrenal response to the stress. Since the pituitary adrenal cortex can respond in a normal way to stress, the low value of MCR of cortisol could be the limiting factor in the adrenal secretion rate of cortisol in estrogen-treated guinea-pigs.