Plasma Glucocorticoid Concentrations Research Articles

Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

Floor Space Needs for Laboratory Mice: C56BL/6 Males in Solid-bottom Cages with Bedding.

Measures of performance, mortality, adrenal weights, plasma glucocorticoid concentration, and selected immune measures were collected in an attempt to define space needs of laboratory mice. Six replications of 3 C57BL/6 male mice per cage were examined while housed on bedding at 5, 10, 15, or 20 in(2) (32.2, 64.5, 96.8, or 129 cm(2)) per mouse. Body weights were not influenced by treatment; however, mice in smaller spaces (5 in(2) per mouse) consumed or wasted more feed and water than mice given greater space allowances. Mice given the least amount of space (5 in(2) per mouse) had greater lymphocyte proliferation in response to the T-cell mitogen PHA than mice given more space. Mice provided 10 in(2) per mouse had greater natural killer cytotoxicity than mice given greater or less space. Mouse mortality was greater as more space was provided. In contrast, adrenal weights and plasma glucocorticoid concentrations were progressively greater with lower space allowances. The National Research Council 1996 recommendation of 15 in(2) per mouse, for this strain and sex of mice, would result in greater mortality and reduced activity of some immune measures. Socially housed male C57BL/6 mice will benefit from less space than recommended by the National Research Council in 1996.

Stress and Adrenal Function in The Platypus (Ornithorhynchus anatinus).

The platypus is a difficult species to maintain in captivity and very few zoo animals attain a natural lifespan. Although the failure of some individuals to acclimatise to captivity appears to be related to stress there have been few studies on the stress response of this species. Preliminary data, that we presented previously, indicated that platypuses exhibited a marked and rapid adrenal response, with catecholamine concentrations being extremely high within 15 minutes of disturbance. Plasma glucocorticoid concentrations also rose rapidly after animals were entangled in nets. This was accompanied by a rise in free fatty acid (FFA) concentrations but no significant change in plasma glucose levels. The latter indicates that the platypus, like the echidna, is resistant to the glucose mobilising effects of glucocorticoids. This paper presents further data to support the earlier findings. In matched sets of blood samples, from individual animals, glucocorticoid concentrations rose from around 100 nmol/L at 15 minutes after entangled in the net, to 300 nmol/L by 65 minutes after disturbance. Dexamethasone treatment caused a marked decline in plasma glucocorticoids, in comparison to untreated control animals, indicating that negative feedback control of ACTH secretion occurs in the platypus. Further, subsequent treatment with ACTH caused a rise in plasma glucocorticoids in comparison to untreated control animals. These data indicate that while the adrenal response in the platypus is very large its control is similar to most other mammals.

Glucocorticoids and the hippocampus. Developmental interactions facilitating the expression of behavioral inhibition.

When threatened, the rapid induction of fear and anxiety responses is adaptive. This article summarizes the current knowledge of the neurobiological development of behavioral inhibition, a prominent response occurring in fear and anxiety-provoking situations. In the rat, behavioral inhibition as exemplified by freezing first appears near the end of the second postnatal week. This emergence of freezing coincides with the developmental period marked by the rapid increase in plasma concentrations of glucocorticoids. Studies show that removal of glucocorticoids at this time severely impairs the age-dependent appearance of freezing. This behavioral impairment produced by adrenalectomy, however, is prevented by exogenous glucocorticoid administration. The effectiveness of glucocorticoids in facilitating the development of freezing appears to be caused by its actions in the hippocampus. In particular, glucocorticoids appear to play a vital role in the postnatal cellular development of the hippocampal dentate gyrus. Doses of glucocorticoids shown to reverse the behavioral inhibitory deficits occurring after adrenalectomy are ineffective when hippocampal dentate granule neurons are destroyed by neurotoxins. Notably, site-specific administration of glucocorticoids to the dorsal hippocampus is successful in promoting the occurrence of freezing in the adrenalectomized rat pup. It is hypothesized that glucocorticoids exert their behavioral inhibitory effects by influencing the development of the septohippocampal cholinergic system. Support for this hypothesis is derived from work demonstrating the importance of glucocorticoids on nerve growth factor systems that play a critical role in septohippocampal cholinergic survival.

Distribution of calbindin-D 28K in the brain of the fetal sheep in late gestation

Immunocytochemical distribution of calbindin-D 28K was examined in the brains of fetal sheep at 100–105 and 120–125 days of gestation (dGA) and at term in labor (term ∼ 150 dGA) and compared to adult sheep. Brains were perfused, cut frozen and immunostained as freely floating sections with a polyclonal anti-calbindin-D 28K antibody. Light microscopy revealed that calbindin-D 28K immunogenicity in fetal cerebellum, rhombencephalon, mesencephalon, diencephalon and telencephalon was overall very similar to that seen in the brains of adult sheep. In addition even though fetal sheep peripheral plasma cortisol concentrations increase 10–20 times over the last 3–4 weeks of gestation to peak during labor and delivery, no glucocorticoid dependent increases in calbindin-D 28K in the hippocampal formation could be seen in the sheep fetus as have been demonstrated for the adult rat given exogenous glucocorticoids. It is concluded that: (1) the basic pattern of calbindin-D 28K distribution seen in adult sheep brains is established by at least 100 dGA in the sheep fetus; and (2) the pattern of calbindin-D 28K expression in fetal sheep hippocampal formation is not related to peripheral plasma glucocorticoid concentrations.

Pancreatic polypeptide enhances plasma glucocorticoid concentration in rats: Possible role in hypoglycemic stress

The acute bolus intraperitoneal (i.p.) administration of pancreatic polypeptide (PP) dose-dependently enhanced the plasma concentration of corticosterone (PBC) in hypophysectomized/ACTH replaced rats, but not that of aldosterone. Minimal and maximal effective doses were 10(-12) and 10(-10) mol/rat, respectively, and maximal PBC increase occurred between 60 and 120 min after PP injection. Insulin (1 U/kg, i.p.) evoked a net decrease in the blood glucose concentration, and marked rises in the plasma levels of PP and PBC, that attained their maximum at 60 and 120 min, respectively. The effects of insulin were annulled by the simultaneous injection of 0.5 mg/kg atropine. The effects of 1 U/kg insulin and 10(-10) mol/rat PP on PBC were not additive; atropine did not affect PBC response to PP or PP plus insulin, though annulling that to insulin alone. Taken together these findings suggest that PP plays a physiologic role in the rat as modulator of the adrenal response to the insulin-induced hypoglycemic stress.

Coping with new social situations: the role of social rearing in guinea pigs

Six colony (CM) and six individually reared males (IM), aged 7 to 8 months, were singly introduced into unfamiliar colonies of conspecifics for a period of 30 days. CM easily adjusted to the new social situation: on the 1st day they explored the new environment but did not court any female thereby avoiding attacks from the male residents. In the course of the following days they gradually integrated into the social network of the established colonies and could even gain higher ranking social positions than those which they had had in their natal colonies. On the CM 1st, 3rd, 6th, 10th and 20th day in the new colonies, changes could not be determined in either their body weights or in their plasma concentrations of glucocorticoids, androgens and norepinephrine. In contrast, IM responded to the new situation with substantial decreases in body weight as well as with extreme increases in plasma glucocorticoid concentrations. We conclude that CM, in comparison to IM, can integrate well into strange colonies be...

Methylprednisolone Achieves Greater Concentrations in the Lung Than Prednisolone: A Pharmacokinetic Analysis

Previous studies in humans and rabbits demonstrated that methylprednisolone appears in the lung in greater concentration than prednisolone. To ascertain which pharmacokinetic properties of these drugs explain this difference, we gave methylprednisolone and prednisolone, 5 mg/kg intravenous bolus, to 23 adult rabbits. To measure the plasma concentration versus time curves for methylprednisolone and prednisolone, samples were obtained predose through 480 min postdose. To measure the bronchoalveolar lavage glucocorticoid concentration versus time curves, lavage was performed once per experiment at seven separate time points from 5 to 480 min post-dose (two to four experiments per time point). Bronchoalveolar lavage fluid (BALF) recovery ranged from 50 to 75% and was similar in both groups. Glucocorticoid concentration in plasma and BALF was determined by high performance liquid chromatography. To normalize for the dilutional effects of lavage, epithelial lining fluid (ELF) recovery was quantitated from BALF volume and BALF and plasma urea concentrations. Pharmacokinetic parameters of the two glucocorticoids were calculated both noncompartmentally and by a three-compartment model. The extrapolated plasma glucocorticoid concentrations at time zero of methylprednisolone and prednisolone are similar, but the volume of distribution and plasma half-life of methylprednisolone are significantly greater than those of prednisolone (p less than 0.05). Although the clearance of the two drugs are not significantly different, methylprednisolone appears to have a slower Cl than prednisolone. The mean residence time (the average time drug remained in body) was significantly longer for methylprednisolone than for prednisolone (p less than 0.05), and plasma glucocorticoid concentrations became significantly different in the two groups by 90 min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH and glucocorticoid responses under two conditions of stress in macaques.

Female macaques were tested under two different psychologically stressful situations in which plasma ACTH and glucocorticoid concentrations were measured. In the first, animals were operantly trained to enter a small transport cage over a four-week period, and plasma ACTH and glucocorticoids were measured in response to brief confinement in the cage before and after training. ACTH values were significantly lower in the pre-test (stress) condition when compared to those for the post-test, whereas the opposite result was found for glucocorticoid values. In the second experiment, blood samples were collected before and one hour after exposure to more acute and severe stress (restraint, venipuncture, handcapture, transport). Both ACTH and glucocorticoid values were significantly elevated from baseline at the post-test sample. The differential relationship between the two hormones among the two experiments was likely the result of the specific timing and magnitude of the stress imposed by each test situation.

Plasma glucocorticoid concentrations in calves as an indicator of stress during parturition

SUMMARY Plasma glucocorticoid concentrations and blood gas values were determined for 6 days in 47 newborn calves that had been subjected to various obstetrical procedures at term. Concentrations of glucocorticoids were uniformly high at birth (70 to 103 ng/ml). Increasing degrees of acidosis were accompanied by increasing glucocorticoid concentrations in plasma. Plasma glucocorticoid concentrations decreased sharply during the first 6 hours after delivery and reached a plateau at 48 hours after birth (14 to 21 ng/ml). The latter was taken as an indication that adaptation had been achieved. Calves subjected to severe pulling had higher glucocorticoid concentrations at birth (110.4 ng/ml) than calves requiring no assistance (88.3 ng/ml), calves requiring only slight assistance (83.8 ng/ml), or calves that had been delivered by cesarean section (82.9 ng/ml).

Plasma concentrations of glucocorticoids in white-tailed deer: the effect of acute ACTH and dexamethasone administration

To study the response of the adrenal gland of white-tailed deer to exogenous ACTH, eight penned animals (five mature intact males, one mature castrate male, one adult castrate female, and one immature female) were sedated with xylazine and ketamine and then challenged with various doses of ACTH with and without dexamethasone (DX) pretreatment. Plasma concentrations of cortisol and cortiscosterone were determined by radioimmunoassay in serial samples taken from a jugular cannula. Rapid, dose-dependent increases lasting over 5 h were observed after intramuscular injection of 10, 20, or 40 IU of porcine ACTH. The ratio of cortisol to corticosterone varied from 2:1 to 40:1. Maximum cortisol concentrations averaged 14.9, 20.3, and 21.3 μg/dL, respectively. Intravenous infusion of 5 mg of DX induced a rapid decline of cortisol levels. Administration of 20 or 40 IU of ACTH 140 min after DX caused increases of cortisol which were not different from those when ACTH was given alone. It was concluded that (i) xylazine and ketamine immobilization is suitable for study of the adrenal activity in deer, (ii) 20 IU of ACTH elicits maximal response of cortisol and corticosterone, (iii) DX pretreatment can result in minimal cortisol concentrations but its use is not essential for studies of adrenal response to ACTH, and (iv) the adrenal response to ACTH of females and castrate males is similar to that of intact males.

Effects of Dystocia on Postpartum Adrenocortical Function in Dairy Cows

Postpartum adrenocortical responses to adrenocorticotropic hormone in cows after normal (n=10) and difficult (n=52) parturition were investigated. The postpartum adrenocortical function of cows was affected by type of parturition (spontaneous parturition, forced extraction of fetus, caesarean section calving with or without attempted forced extraction, and total fetotomy) and day after calving (d 1, 4, and 8; d 0 = day of parturition). Cows after normal calving did not show enhanced or depressed adrenocortical function postpartum. Adrenocortical function was enhanced, compared with cows calving normally, for cows with dystocia that had a caesarean section after forced extraction was attempted and in cows in which calves were already dead and total fetotomy was performed. Cows with dystocia assisted with forced extraction by one to two people and cows that had caesarean sections without forced extraction did not show higher plasma glucocorticoid concentrations before or after adrenocorticotropic hormone administration than did cows with normal calving. Results indicate that dystocia requiring caesarean section following unsuccessful extraction or total fetotomy enhanced postpartum adrenocortical function in cows.

Failure of glucocorticoid feedback during breeding in the male red-tailed phascogale Phascogale calura (Marsupialia: Dasyuridae)

An investigation was made into the factors which lead to an elevation in plasma free cortisol concentration during the last weeks of life of males in natural populations of the red-tailed phascogale Phascogale calura. The dexamethasone suppression-test was employed to examine the glucocorticoid feedback control of plasma cortisol both before and during the breeding season. In both sexes ACTH alone or in combination with dexamethasone caused an elevation in the plasma concentration of cortisol, corticosterone and free cortisol. Dexamethasone administration in both males and females resulted in significant decreases in the plasma concentration of each of the glucocorticoid groups both before and during the first week of the breeding season (June and early July), however during the last week of breeding (late July) dexamethasone decreased the plasma glucocorticoid concentration of females but not of males. Administration of ACTH caused a significant elevation in the plasma cortisol concentration in all groups. However, the magnitude of this response diminished with time in both sexes. Dexamethasone treatment resulted in a decrease in the plasma testosterone concentration in males before and early in the breeding season however toward the end of breeding this effect was abolished. It is apparent that towards the end of the breeding season and during the last week of life of the males, glucocorticoid feedback control of ACTH is almost abolished. These changes, which occur only in the males late in the breeding season and near the time of their disappearance from the population, are consistent with a condition known as end organ resistance to steroid hormones.

Adrenocortical Function in Cows with the Downer Cow Syndrome A Preliminary Report

To find out if cows with the downer cow syndrome have enhanced or exhausted adrenocortical function, fifteen downer cows were examined for adrenocortical response to 25 IU of adrenocorticotropic hormone (ACTH) between 1 and 9 days postpartum. Of the 15 cows, only two cows recovered following treatment, 10 cows were slaughtered due to poor prognosis and 3 cows were found dead. Four cows with milk fever also were investigated for adrenocortical function. Both the downer cows and cows with milk fever had significantly higher basal and ACTH-stimulated plasma glucocorticoid concentrations than cows without any postpartum complications on day 1 to 2 postpartum (P less than 0.05). There was a tendency that the downer cows which recovered later did not show enhanced adrenocortical function on day 4 to 5 and day 7 to 9 postpartum, while the downer cows with poor prognosis had significantly enhanced adrenocortical activity on the same days postpartum. The enhanced adrenocortical function shown in the milk fever cows on day 1 to 2 postpartum returned to a nearly normal state after their recovery. The results indicate the downer cows with poor prognosis had greatly enhanced adrenocortical function.

Glucocorticoids and the differentiation of porcine preadipocytes.

The function of glucocorticoids in the differentiation of porcine preadipocytes was examined. Stromal-vascular cell cultures (containing preadipocytes) derived from adipose tissue of the perirenal, ham and shoulder regions of neonatal pigs were incubated in the presence of hydrocortisone at 0 to 100 ng/ml medium. Perirenal cells did not respond to hydrocortisone with an increase in enzyme expression, nor did they demonstrate growth characteristics similar to those of cultures derived from the ham or shoulder. Cultures from the shoulder and ham regions demonstrated dose-responsive increases in enzymatic expression to hydrocortisone. Enzymatic responses by cultures derived from the ham region were lower than responses by cultures from the shoulder region as measured by changes in the activities of sn-glycerol-3-phosphate dehydrogenase and lipoprotein lipase. Addition of insulin to the medium did not produce a synergistic effect with glucocorticoid on differentiation as determined by these enzymatic parameters. However, [14C]glucose metabolism by the cells in culture was synergistically increased by insulin and glucocorticoid supplementation of the medium. The ability of hydrocortisone to induce differentiation of porcine preadipocytes in vitro suggests that the changes that occur in plasma glucocorticoid concentrations during late gestation may play an important role in the rapid development of s.c. adipose tissue in the fetal pig. Secondly, the differences in culture characteristics and hormone responses of cells derived from different locations of adipose tissue formation indicate that differences may exist in the regulation of the growth and development of preadipocytes from different anatomical locations.

Effects of chronic alprazolam treatment on plasma concentrations of glucocorticoids, thyroid hormones, and testosterone in cardiomyopathic hamsters

In the first of two experiments, young male cardiomyopathic hamsters were injected intraperitoneally twice a day for 29 days with 8 mg alprazolam/kg body weight or saline. Three hours after the same injections on day 30, they were sacrificed and plasma hormone levels were measured. Alprazolam increased cortisol, total glucocorticoid and triiodothyronine levels. It did not affect corticosterone, thyroxine or testosterone levels. The same protocol was used in a second experiment, except the controls received vehicle and a third group was treated with 48 mg diazepam/kg body weight. Alprazolam again increased cortisol and total glucocorticoid levels, but not those of corticosterone. On the other hand, diazepam increased both cortisol and corticosterone levels. These experiments suggest that chronic benzodiazepine treatment can affect adrenocortical function and perhaps some aspects of thyroid function.

Glucocorticoid influences on the auditory brain-stem responses in man

The present study was designed to test whether human auditory brain-stem responses (ABRs) are sensitive to peripheral endocrine signals as reflected by changes in the plasma glucocorticoid concentration. ABRs were recorded following treatment with 50 mg hydrocortisone or placebo in 13 healthy male adults. Experiments were double-blind and designed according to a latin-square within-subject comparison. Treatment was applied 1 h prior to testing as an i.v. infusion over a period of 20 min. Subjects were tested in each session under 3 X 3 conditions, i.e., ABRs were obtained to series of clicks presented at 3 different intensities (80, 60, 40 dB HL) and with 3 different stimulus rates (39, 10, 5 clicks/sec). Additionally, oral temperature was monitored. Hydrocortisone significantly reduced latencies of waves III, V, and VI (and subsequent negative troughs) when low stimulus intensities were used. Furthermore, the glucocorticoid reduced latencies of waves Vn, VI and VIn when the clicks were presented at a slow stimulus rate. Further studies have to specify the underlying mechanisms of these changes.

Vasopressin: a regulator of adrenal glucocorticoid production?

Vasopressin infusion has been shown to decrease plasma adrenocorticotropic hormone (ACTH) concentration and transiently increase plasma cortisol concentration in conscious dogs. In the present study, one experiment tested the hypothesis that vasopressin infusion decreases ACTH by activation of a V1 receptor mechanism, e.g., by increasing atrial pressures and stimulating the low-pressure baroreceptor reflex. Administration of a vasopressin V1 antagonist eliminated the increases in atrial pressure and decreases in heart rate with vasopressin infusion (1 ng.kg-1.min-1), as it eliminated the decrease in ACTH, which is consistent with baroreflex-mediated inhibition of ACTH by vasopressin. A second experiment evaluated the role of ACTH in the increase in glucocorticoids. Dexamethasone pretreatment, which inhibits ACTH secretion, abolished the increase in glucocorticoid concentration with vasopressin infusion, indicating that ACTH is necessary for the glucocorticoid response. A third experiment was performed to determine whether the glucocorticoid response could be restored in dexamethasone-treated dogs, when ACTH concentration was maintained near control levels by intravenous infusion of synthetic alpha-ACTH-(1-24) (0.3 ng.kg-1.min-1). In these dogs, vasopressin infusion produced a sustained increase in plasma glucocorticoid concentration from 22 +/- 3 to 49 +/- 8 ng/ml (P less than 0.001). Infusing higher levels of ACTH (0.5 ng.kg-1.min-1) enhanced basal glucocorticoid levels but did not enhance the response to vasopressin. Vasopressin infusion did not alter clearance of glucocorticoids. Collectively, these results suggest that vasopressin directly stimulates adrenal glucocorticoid production, provided that background levels of ACTH are present.

Vasopressin and ANG II in the control of ACTH secretion and arterial and atrial pressures

Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.

Factors involved in the regulation of adrenocorticotropic hormone/beta-lipotropic hormone.

Factors involved in the regulation of adrenocorticotropic hormone/beta-lipotropic hormone.