Effects of ethanol on the concentration of neuropeptides, ACTH and corticosterone during immobilization stress

It was shown, that stress increased the level of ACTH, beta-endorphin and corticosterone in the blood plasma of the rat. Injection of ethanol (1 g/kg) decreased the level of ACTH, but increased the levels of beta-endorphin in the rat subjected to immobilization stress. The immobilization lowered the levels of met-enkephalin in the striatum and medulla oblongata, but increased the content of neuropeptide in the adrenal glands. The concentration of leu-enkephalin and DSIP remained unchanged following the stress. Ethanol reversed the action of immobilization on the level of met-enkephalin in the striatum, but increased the content of DSIP in the thalamus. These results indicate that ethanol modified the activity of pituitary-adrenal-axis during stress and probably the stress-protective action of ethanol partly performed with the involvement of DSIP.     

Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats

A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress.     

Basis for the use of Pierre's method for the determination of ACTH in human blood plasma]

Adrenal glands of rats were immersed in Ringer-Lock solution (used as control), other rat adrenal glands were immersed in human blood plasma. The amount of corticosterone in the extracts received was estimated after two hours of incubation. The activity of adrenocorticotropic function of the pituitary gland of the patients examined was judged by the difference in the corticosterone indices in these extracts. ACTH (1.5 and 10 mkg) was added to the plasma to determine the sensitivity of this technique. Regular and significant increase in corticosterone was revealed. Modified Pierre's technique can be applied for ACTH determination in man.     

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.     

Detection of the pro-opiomelanocortin peptide fragments--beta-endorphin and ACTH--in the adrenals of rats and mice by immunohistochemistry

Independent peptide fragments of pro-opiomelanocortin molecule, beta-endorphin and ACTH, have been detected immunohistochemically in the adrenal glands of rats and mice. Immunoreactive beta-endorphin and ACTH have been revealed in the adrenal medulla and reticular zone of the adrenal cortex. beta-endorphin and ACTH distribution patterns in adrenal sections were identical, which is indicative of the linked synthesis of these peptides in the adrenal gland. The data obtained suggest the existence of pituitary-independent mechanisms regulating corticosteroidogenesis in the adrenal gland, involving adrenal pro-opiomelanocortin fragments.     

Hypertrophy and altered activity of the adrenal cortex in Homer 1 knockout mice

Homer 1 gene products are involved in synaptic transmission and plasticity, and hence, distinct behavioral abnormalities, including anxiety- and depression-like behaviors, have been observed in Homer 1 knockout (KO) mice. Here we report that Homer 1 KO mice additionally exhibit a pronounced endocrine phenotype, displaying a profoundly increased adrenal gland weight and increased adrenal/body weight ratio. Histological examinations of Homer 1 deficient adrenal glands revealed an increased size of the adrenal cortex, especially the sizes of the zona fasciculata and zona glomerulosa. Moreover, the plasma corticosterone and aldosterone were higher in Homer 1 KO than wild-type (WT) mice while the plasma ACTH levels were not different between the genotypes. The in vivo ACTH test revealed that corticosterone and aldosterone plasma levels were higher in saline injected Homer 1 KO mice than in WT mice (saline injected mice served as controls for the respective groups of ACTH-injected animals), but the magnitude of steroid responses to ACTH was similar in both genotypes. In contrast, an in vitro experiment performed on isolated cells of adrenal cortex clearly showed increased production of both steroids in response to ACTH in Homer 1 KO cells, which is in line with an ~8-fold increase in the expression of ACTH receptor mRNA in the adrenal cortex of these mutants. These results, together with the detection of Homer 1 mRNA and protein in the adrenal cortex of WT mice, indicate that Homer 1 directly affects the steroidogenic function of the adrenal glands.     

The effect of hydra peptide morphogen on the levels of beta-endorphin and some blood and adrenal hormones in albino rats]

The influence of PMH on the level of beta-endorphin and some hormones of blood and adrenal glands was studied. The dose A (10 mkg/kg) and dose W (100 mkg/kg) of PMH were used in our experiments. Earlier it has been discovered, that PMH in such doses stimulated the processes of cell division in 24 hours since the moment of injection. The stimulation was dose-dependent. Within 24 hours PMH in A dose decreased the concentration of beta-endorphin in the blood 2.7-fold, ad in dose W increased it 2 times. The level of corticosterone in blood and adrenal glands after the injection of PMH in dose A exceeded the control data trustworthy in 4 and 24 hours since the moment of injection. In dose B in 4 hours 1.5-fold reduction of corticosterone concentration took place in the blood. Increase in epinephrine level in adrenal glands was observed after PMH administration in two doses. Content of T3 increased in 4 hours after PMH injection in dose B. The role of hormonal changes in stimulating cell division accompanied by PMH injection is discussed. The data received show that PMH influences directly proliferative processes.     

Antioxidant ionol suppresses ACTH-dependent secretion of corticosterone

It has been shown that the preliminary administration of a synthetic antioxidant ionol (dibunol, BHT) prevented to a considerable extent the increase in the concentration of corticosterone in the adrenal glands and blood plasma induced by ACTH administration or emotional-painful stress.     

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.     

ACTH, corticosterone and beta-endorphin in the blood plasma of rats under prolonged immobilization stress

Radioimmunoassays were employed to study variation in the concentration of corticosterone, ACTH and beta-endorphin in rat blood plasma at different times of the 30-hour immobilization and under the effect of a short-term action of ecologically significant negative stimulation emanating from other animals. Both prolonged immobilization stress and short-term emotional reaction produced appreciable alterations in the blood plasma content of all the hormones under study. The findings indicate that variations in the corticosterone and beta-endorphin levels were in the best agreement.     

Cocaine induced secretion of ACTH, beta-endorphin, and corticosterone

The effect of intraperitoneal administration of cocaine on the concentrations of hypothalamic corticotropin releasing factor like-immunoreactivity (CRF-LI), plasma ACTH, beta-endorphin, and corticosterone was investigated. Groups of rats were injected with 20 mg/kg cocaine HCI or 0.9% NaCl and then killed 0, 10, 20, 30 or 60 minutes later. Hypothalamic CRF-LI, plasma ACTH, beta-endorphin, and corticosterone concentrations were determined by radioimmunoassay. A significant increase in plasma ACTH, beta-endorphin, and corticosterone concentrations was observed after cocaine administration. In contrast, cocaine had no significant effect on hypothalamic CRF-LI concentrations. Intravenous administration of 0.5 and 2.0 mg/kg cocaine to rats in which the endogenous release of CRF was blocked by chlorpromazine, morphine, and pentobarbital elicited a significant increase in plasma corticosterone concentrations. These results demonstrate that cocaine induces the release of ACTH, beta-endorphin, and corticosterone and suggest that this response is mediated at the pituitary level.     

Effects of cortisol treatment on brain and adrenal corticotropin-releasing hormone (CRH) content and other parameters regulated by CRH

Corticotropin-releasing hormone (CRH) has been found in both hypothalamic and extrahypothalamic sites of the brain and also in the adrenal medulla. To study the timing and location of delayed glucocorticoid action in rats, we measured the effects of 2-day and 7-day cortisol treatment on immunoreactive CRH concentrations in hypothalamus, cerebral cortex, hippocampus, cerebellum, and adrenal gland. The activity of the hypothalamo-pituitary-adrenal (HPA) axis and the sympathoadrenal system were also measured. Studies were carried out both in the afternoon and/or in the morning, to get information about possible circadian changes. CRH contents were not changed in any brain areas studied, except there was a trend of decrease in the hypothalamus compared to vehicle in the afternoon due to the lack of circadian increase after 7-day cortisol treatment. Pituitary ACTH content decreased significantly after 7-day treatment, while beta-endorphin did not. Plasma levels of ACTH, corticosterone, norepinephrine and epinephrine and adrenal ACTH and beta-endorphin contents decreased after 2-day, adrenal CRH content after 7-day treatment with cortisol. Our findings suggest, that chronic cortisol treatment inhibits the circadian activation of the HPA axis at all levels but has variable effects on baseline measures because it causes different changes in release and synthesis at different sites.     

Effect of synthetic atrial natriuretic polypeptide on hemorrhage-induced adrenocorticotropin secretion of the rat

The effect of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on the in vivo and in vitro release of ACTH and corticosterone was examined. In the in vivo study ACTH and corticosterone responses to rapid 2-ml/rat hemorrhage were measured in sixteen conscious rats after alpha-hANP administration. The hemorrhage increased plasma ACTH and corticosterone concentrations in the control group of rats (p greater than 0.01). ANP inhibited hemorrhage-induced ACTH secretion (p less than 0.05), but the plasma corticosterone response was not affected. In the in vitro study a high concentration of ANP (1 microM) reduced basal corticosterone secretion from the isolated rat adrenal gland (p less than 0.05), but the response to ACTH (10 ng/ml) and dibutyryl cyclic AMP (0.5 mM, 5.0 mM) was not affected. Our data suggest that ANP inhibits hemorrhage-induced ACTH secretion from the anterior pituitary but inhibits corticosterone secretion from the adrenal gland very weakly.     

Sex differences in adrenocortical structure and function. XXVIII. ACTH and corticosterone in intact, gonadectomised and gonadal hormone replaced rats

Plasma ACTH and corticosterone (B) concentration, ACTH content in the anterior pituitary gland and B content in the adrenals were measured in intact, gonadectomised and testosterone or estradiol replaced rats. Plasma ACTH and B levels and adrenal B content were higher in female than male rats. Neither orchiectomy nor testosterone replacement had an effect on plasma ACTH and B concentration. Orchiectomy did not affect adrenal B content and decreased pituitary ACTH while testosterone significantly lowered ACTH and B content in studied glands. On the other hand ovariectomy did not change pituitary ACTH and adrenal B content and notably lowered concentrations of these hormones in the blood. Estradiol replacement resulted in an increase in plasma ACTH and B concentrations, an effect accompanied by a marked drop in pituitary ACTH and an increase in adrenal B. These findings indicate the distinct sex differences in basal plasma ACTH and B concentrations with higher values in female rats, an effect dependent on the stimulatory action of estradiol on pituitary-adrenocortical axis.     

ACTH stimulation of adrenal epinephrine and norepinephrine release

Epinephrine (E) and norepinephrine (NE) levels were measured simultaneously in the adrenal veins of 6 patients before and after stimulation with 0.25 mg beta 1-24 ACTH. In 1 patient with Cushing's syndrome, E and NE were also measured before and 30 min after dexamethasone. There was a significant increase in NE and E secretion (p less than 0.002) from both adrenal glands after ACTH stimulation. In the patient with Cushing's syndrome, there was also a slight increase in plasma E levels after dexamethasone. It is postulated that ACTH stimulated NE and E secretion by augmenting blood flow through the adrenals and by induction of tyrosine hydroxylase and dopamine beta-hydroxylase, although a direct effect of ACTH on NE and E secretion cannot be excluded. It is also possible that the increase in adrenal catecholamine secretion after ACTH may be due to ACTH augmentation of catecholamine secretion by endogenous opioids such as beta-endorphin.     

Relationship between corticosterone and body weight,androstenedione and insulin during the period of delayed ovulation in a vespertilionid bat,Scotophilus heathi

The aim of the present study was to evaluate the relationship between corticosterone, body weight, insulin and androstenedione in order to understand the role of adrenal in contributing hyperandrogenism during delayed ovulation in S. heathi. The circulating corticosterone concentration in female S. heathi showed significant seasonal variation. The peak corticosterone concentration observed during August-September coincides with increased feeding activities in S. heathi. The present study noted a seasonal variation in relationship of corticosterone with insulin and androstenedione in S. heathi. An inverse relationship of corticosterone with insulin and androstenedione was found during August to December, but not during January to May. A seasonal variation in the effect of adrenocorticotropic hormone (ACTH) on adrenal corticosterone production in vitro was observed during reproductive cycle. Corticosterone production in vitro by adrenal declined significantly as compared to the control during quiescence in September. The finding suggests that adrenal attained the peak responsiveness to ACTH during September. ACTH significantly enhanced the androstenedione production by the adrenal in vitro during December, when the circulating androstenedione was also high in S. heathi. This suggests that the adrenal may also contribute to hyperandrogenism during the period of delayed ovulation in S. heathi. Further studies are required to reveal the unique pattern of seasonal relationship between corticosterone, insulin and androstenedione in S. heathi.     

Adrenocortical responses to adrenocorticotrophin in the rat

The time course of plasma adrenocorticotrophin (ACTH), adrenal cyclic AMP, adrenal corticosterone, and plasma corticosterone was measured in male Sprague-Dawley rats whose endogenous release of ACTH had been blocked (1) following rapid injections of 100 and 300 ng ACTH/100 g body weight, i.v., (2) during prolonged infusions at rates of 1, 2, and 4 ng ACTH/min per 100 g body weight, and (3) after termination of 30-min infusions at rates extending from 0.06 to 8 ng ACTH/min per 100 g body weight. Following injections, the time course of the variables is similar to the one simulated from our models of adrenal cortical secretion, including the simulation of an intermediate variable of our models of the adrenal cortex cell which was presumed to correspond to cyclic AMP. However, during prolonged infusions there is an unexpected overshoot of adrenal cyclic AMP content whereas adrenal and plasma corticosterone concentrations rise to a steady-state value without overshoot. The total amount of cyclic AMP gradually increases following the three increasing infusion rates of ACTH whereas similar levels of plasma corticosterone concentrations are reached at steady state; therefore the saturation of the adrenal cortical secretion is due to a step ulterior to cyclic AMP formation in the steroidogenesis. After 30-min infusions, plasma corticosterone concentration reaches its maximal value following a rate of ACTH input which evokes only a 4-fold increase in adrenal cyclic AMP content; however, there is a 250-fold increase of adrenal cyclic AMP with respect to control value following the higher rates of infusion of ACTH.     

The met-enkephalin and beta-endorphin content of the blood in the early period after acute blood loss in rats

The experiments have been performed on 164 rats and 110 mice. Met-enkephalin and beta-endorphin concentration was established to increase in the blood in the early period after acute blood loss in rats who survived after 24 hours of a follow up in the group of animals, who died during 24 hours follow up, the momentary beta-endorphin increase was noted at the 1st minute of the experiment; met-enkephalin contents in blood wasn't essentially changed. mu-Receptors' agonist DAGO injection significantly decreased rat mortality in a posthemorrhagic period. The correlation between arterial pressure values and beta-endorphin and met-enkephalin contents in the blood wasn't defined. The opioid peptides' ability to increase the organism stability to hypoxia was determined. Beta-endorphin and met-enkephalin significance in the pathogenesis of a posthemorrhagic period in acute blood loss is being discussed.     

Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function

Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and flutamide (25 mg/kg body wt) was administered subcutaneously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone, as well as adrenal corticosterone and cAMP were measured 20 h after resuscitation. In additional animals, ACTH was administered and ACTH-induced corticosterone release and adrenal cAMP were determined. The results indicate that adrenal contents of corticosterone and cAMP were significantly decreased and morphology was altered after hemorrhage. Administration of flutamide improved corticosterone content, restored cAMP content, and attenuated adrenal morphological alterations. Flutamide also improved the diminished ACTH-induced corticosterone release and adrenal cAMP response at 20 h after hemorrhage and resuscitation. Furthermore, the diminished corticosterone response to ACTH stimulation in the isolated adrenal preparation was improved with flutamide. These results suggest that flutamide is a useful adjunct for improving adrenal function in males following trauma and hemorrhage.