Showing papers on "Corticosterone published in 1991"
TL;DR: It appears that brain membranes contain a corticosteroid receptor that could participate in the regulation of behavior, and these binding sites were localized by receptor autoradiography in the neuropil, outside the regions of perikarya.
Abstract: Steroids may rapidly alter neuronal function and behavior through poorly characterized, direct actions on neuronal membranes. The membrane-bound receptors mediating these behavioral responses have not been identified. [3H]Corticosterone labels a population of specific, high-affinity recognition sites (dissociation constant = 0.51 nanomolar) in synaptic membranes from an amphibian brain. These binding sites were localized by receptor autoradiography in the neuropil, outside the regions of perikarya. The affinities of corticoids for this [3H]corticosterone binding site were linearly related to their potencies in rapidly suppressing male reproductive behavior. Thus, it appears that brain membranes contain a corticosteroid receptor that could participate in the regulation of behavior.
531 citations
TL;DR: The hypothesis that the hypothalamic-pituitary-adrenal axis of the neonatal rat is subject to maternal regulation is supported.
Abstract: Prolonged (i.e., 24-hr) maternal deprivation leads to a marked disinhibition of the infant rat's adrenocortical response to stress and/or ACTH. In the following study we examined the time course over which these effects develop. Pups were maternally deprived for varying lengths of time (i.e., 0, 2, 4, 8, & 24 hr); at the end of this period, corticosterone (CORT) secretion in response to stress (novelty or novelty plus saline injection) and ACTH injection was measured. Basal levels of CORT increased progressively over time in 7- and 11- (but not 3-) day-old pups. CORT release in response to stress followed a similar pattern. In contrast, ACTH injection resulted in marked increases in CORT levels regardless of the length of maternal deprivation in 3-day-old animals; at older ages, however, 24 hr of deprivation led to a much larger increase. These findings support the hypothesis that the hypothalamic-pituitary-adrenal axis of the neonatal rat is subject to maternal regulation.
344 citations
TL;DR: Microdialysis was employed to assess extracellular dopamine from medial prefrontal cortex, nucleus accumbens, nucleus caudatus, and acetylcholine from the hippocampus of conscious rats during and after 120 min restraint stress, finding that Adrenalectomized rats responded to stress and liberation in much the same way as intact rats.
342 citations
TL;DR: A sensitive assay based on the polymerase chain reaction demonstrated that the product of CYP11B2 is required for the final steps in the synthesis of aldosterone.
Abstract: The steroid 11 beta-hydroxylase (P450c11) enzyme is responsible for the conversion of 11-deoxycortisol to cortisol in the zona fasciculata of the adrenal cortex. Animal studies have suggested that this enzyme or a closely related isozyme is also responsible for the successive 11 beta- and 18-hydroxylation and 18-oxidation of deoxycorticosterone required for aldosterone synthesis in the zona glomerulosa. There are two distinct 11 beta-hydroxylase genes in man, CYP11B1 and CYP11B2, which are predicted to encode proteins with 93% amino acid identity. We used a sensitive assay based on the polymerase chain reaction to analyze the expression of the CYP11B1 and B2 genes. Transcripts of CYP11B1 were detected at high levels in surgical specimens of normal adrenals and also in an aldosterone-secreting adrenal tumor. Transcripts of CYP11B2 were found at low levels in normal adrenals, but at a much higher level in the aldosterone-secreting tumor. CYP11B2 mRNA levels were increased in cultured zona glomerulosa cells by physiological levels of angiotensin-II. The entire coding regions of both CYP11B1 and B2 cDNAs were cloned from the tumor mRNA. Expression of these cDNAs in cultured COS-1 cells demonstrated that the CYP11B1 product could only 11 beta-hydroxylate 11-deoxycortisol or deoxycorticosterone, whereas the CYP11B2 product could also 18-hydroxylate cortisol or corticosterone. A small amount of aldosterone was synthesized from deoxycorticosterone only in cells expressing CYP11B2 cDNA. These data demonstrate that the product of CYP11B2 is required for the final steps in the synthesis of aldosterone.
339 citations
TL;DR: The relative potencies of the cytokines IL-1, IL-6 and tumor necrosis factor (TNF), which share several biological actions, for stimulating ACTH and corticosterone output in freely-moving rats support the existence of an immune-HPA axis circuit.
278 citations
TL;DR: In this article, male tree lizards (Urosaurus ornatus) were subjected to two forms of stress: acute stress and chronic stress and the response to the acute stress was much greater for both hormones than to the chronic stress, although in both cases testosterone levels changed less in response to stress than corticosterone levels.
274 citations
TL;DR: The data suggest that early handling permanently alters CNS systems that regulate hypothalamic-pituitary-adrenal (HPA) function, although the effect may depend on the gender of the animal.
257 citations
TL;DR: The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life, and these studies were designed to test the functional activation of the HPA axis after a single or repeated exposures to stress.
Abstract: The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life. Although we previously found full responsiveness of the hypothalamus- pituitary unit to adrenalectomy in young rats [days (d) 5-10], we failed to measure a significant increase in ACTH 10 min after ether administration until dl4 of age. These studies were, therefore, designed to test the functional activation of the HPA axis after a single or repeated exposures to stress. Both qualitative (time-course, stressor-specific, circadian) and quantitative changes in the ACTH and corticosterone (B) responses to various stressors were tested during the first 10 days of life. Exposure to 3 min of ether vapor increased ACTH and B secretion (P <0.05–0.01) in 1-, 5-, and 10-d-old rats, with an increasing amplitude of both ACTH and B responses as a function of age. Peak secretion of ACTH occurred 5 min after the onset of stress (122 ± 3.8 to 359 ± 54 pg/m...
257 citations
TL;DR: Observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death, in the rat dentate gyrus, which is characterized by very low levels of adrenal steroids.
Abstract: The rat dentate gyrus undergoes a period of naturally occurring cell death during the first postnatal week. In the adult rat, removal of circulating adrenal steroids by adrenalectomy is followed by massive death in the granule cell layer, thus raising the possibility that developmental cell death results from low levels of these hormones. Interestingly, the first two postnatal weeks of life in the rat, termed the stress hyporesponsive period, are characterized by very low levels of adrenal steroids. In order to determine whether low levels of adrenal steroids enable developmental cell death to occur in the dentate gyrus, we examined the density of pyknotic and healthy cells in the dentate gyrus of rat pups which received one of the following treatments: (1) injections of the endogenous rat glucocorticoid corticosterone during the first postnatal week, or (2) adrenalectomy at the time when glucocorticoid levels normally rise. Quantitative analysis of the density of pyknotic cells in the granule cell layers revealed significant decreases with corticosterone treatment by the end of the first postnatal week. In these same brains, treatment with corticosterone resulted in a substantial increase in the density of pyknotic cells in the hilus. Adrenalectomy resulted in a significant increase in the density of pyknotic cells in the granule cell layer as well as in the hilus. Despite the dramatic alterations in the density of pyknotic cells with both increases and decreases in glucocorticoid levels, the density of healthy cells remained the same. These observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death.
250 citations
TL;DR: The results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes.
Abstract: The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes.
242 citations
TL;DR: The results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.
Abstract: Unlike the majority of mammalian brain regions, the rat dentate gyrus undergoes maximal cell birth and cell death during the same developmental time period. Granule cell birth and death peak at the end of the first postnatal week. We have found that manipulations of glucocorticoid levels during the stress hyporesponsive period profoundly influence the density of pyknotic cells in the dentate gyrus while apparently not affecting the density of healthy cells. This raises the possibility that glucocorticoids are regulating processes in addition to cell death, i.e., cell birth. In order to determine whether increases in circulating glucocorticoids or mineralocorticoids affect the birth of cells in the developing dentate gyrus, 3H-thymidine autoradiography was performed on brains of rat pups treated with either corticosterone or aldosterone during the first postnatal week. Quantitative analysis of 3H-thymidine-labelled cells revealed significant decreases in the density of labelled cells in the granule cell layers with both corticosterone and aldosterone treatment. In these same brains, significant decreases in the density of pyknotic cells were also observed in the granule cell layers. However, no changes in the numbers of 3H-thymidine-labelled pyknotic cells were observed with any treatment. Increases in circulating corticosterone or aldosterone resulted in significant increases in the density of both 3H-thymidine-labelled and pyknotic cells in the hilus. These results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.
TL;DR: The results confirm previous studies that demonstrate the importance of the central amygdaloid nucleus in the expression of corticosterone to immobilization stress and show that neurons within the central amygdala are necessary for the full expression of conditioned stress-induced increase in cortic testosterone and renin secretion.
Abstract: The purpose of this study was to examine the contribution of the central nucleus of the amygdala to the expression of stress-induced increase in corticosterone and renin secretion. Neurons in the cent
TL;DR: The data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.
Abstract: Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20-min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABAB agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABAB and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.
TL;DR: In this article, the same authors compared the brain, pituitary and immune system of rats in the presence or absence of several replacement doses of corticosterone, and found that the lowest replacement dose (equivalent to resting levels of this hormone) blocked this Type II receptor up-regulation, while higher replacement doses were associated with widespread Type I and Type II adrenal steroid receptor down-regulation.
TL;DR: Analysis of stress-induced hormone fluctuations over time indicated that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.
TL;DR: 11 beta-OHSD is appropriately sited to modulate access of corticosterone to vascular receptors and could influence vascular resistance, cardiac output and thereby blood pressure.
Abstract: The enzyme 11β-hydroxysteroid dehydrogenase (11β-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in the rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. We have previously demonstrated that cortisol-induced cutaneous vasoconstriction in man is potentiated by the 11β-OHSD inhibitor glycyrrhetinic acid, suggesting that 11β-OHSD may protect vascular corticosteroid receptors. In this study we report quantitation of 11β-OHSD bioactivity in homogenates of rat aorta, mesenteric artery, caudal artery, and heart, expressed as the percent in vitro conversion of 3H-corticosterone to 3H-ll-dehydrocorticosterone. Nicotinamide adenine dinucleotide phosphate (NADP+)-dependent 11β-OHSD activity was found in all of these tissues and was significantly higher in resistance vessels than aorta (P < 0.05) [without NADP+: caudal artery (4.2 ± 0.2%) = mesenteric...
TL;DR: Results indicate that IL-1 alpha and IL-2 directly stimulate glucocorticoid synthesis in a dose- and time-dependent manner, and the low effective concentrations of both cytokines suggest possible physiological or pathophysiological roles of circulating cytokines in the glucocORTicoidogenesis under certain conditions.
Abstract: The effects of interleukins on adrenal steroidogenesis and their mode of action were studied using cultured rat adrenal cells. The addition of rat interleukin-lα (IL-lα) or rat IL-2 increased corticosterone levels in the medium in a concentration- dependent manner during 24 h of incubation. The minimum, half-maximum, and maximum effective concentrations of both rat IL-lα and rat IL-2 were almost same (-3, 10, and 100 U/ml, respectively). After a latent period, the effect became apparent after 12 h of incubation. Human IL-1β and human IL- 6 also showed a stimulatory effect on corticosterone production, whereas human IL-2 was inactive in this system. To clarify the cellular mechanism of these stimulatory effects, we measured the levels of prostaglandin E2 (PGE2) and cAMP in the cells and media as well as the corticosterone levels. Corticosterone production stimulated by IL-lα or IL-2 was accompanied by intracellular and extracellular cAMP and PGE2 accumulation. Although the stimulation of both cAMP and cort...
TL;DR: It is concluded that the diurnal rhythm in stress responsiveness and, in the PM in the ADX rats, the decrease in plasma ACTH during stress, are largely independent of B.
Abstract: To test whether the diurnal rhythm in stress responsiveness is dependent on corticosterone (B)-mediated negative feedback, the responses of intact (SHAM) and adrenalectomized (ADX) rats to restraint for 3–90 minutes or ip injection with saline in the morning (AM) and the evening (PM) were compared. In both SHAM and ADX rats, ACTH responses to restraint stress were larger in the AM. In intact rats, this could have resulted from both fast negative feedback, due to the rate of rise of B during the stress in the PM, and delayed negative feedback, due to the high basal concentrations of B before the stress in the PM. However, this diurnal pattern of stress responsiveness was not dependent on B, as the same relative responses to restraint and ip injection were found in ADX rats. To determine whether the lack of response of ADX rats in the PM to stress was due to a loss of sensitivity to endogenous secretagogues, ADX rats were given CRF + arginine vasopressin (AVP) while anesthetized with ether after 30 min of r...
TL;DR: IL-1β was found to dose-dependently raise corticosterone (B) blood concentration in hypophysectomized rats, without inducing any significant increase in the level of circulating ACTH, and the secretory effect of IL-1 β was completely blocked by both α-helical-CRF and corticotropin-inhibiting peptide.
Abstract: Interleukin-1 (IL-1), a monokine released by activated monocytes during the acute phase of the inflammatory responses, has been reported to enhance hypophyseal ACTH release mainly by stimulating hypothalamic CRF secretion We investigated a possible direct effect of IL-1β on the adrenal gland of the rat IL-1β was found to dose-dependently (4–8 μg/kg) raise corticosterone (B) blood concentration in hypophysectomized rats, without inducing any significant increase in the level of circulating ACTH IL-1β did not affect B production by either isolated rat inner adrenocortical cells or fragments of adrenocortical autotransplants lacking chromaffin cells, but dose-dependently (10−8-10−6 M) enhanced that by adrenal slices including both cortex and medulla The secretory effect of IL-1β (10−6 M) was completely blocked by both α-helical-CRF (10−6 M) and corticotropin-inhibiting peptide (10−6 M), two competitive inhibitors which (at these concentrations) were able to annul B response of adrenal slices to CRF (10−6
TL;DR: This study demonstrates that in addition to an acute inhibition of precursor growth, glucocorticoids exert a clear stimulation of adipose conversion, which depends mainly on the presence of insulin and the glucoc Corticoid concentration.
TL;DR: Results suggest that the increase in GFAP resulting from ADX is not mediated through an injury‐linked mechanism, and glucocorticoids and injury appear to regulate the expression of GFAP through different mechanisms.
Abstract: Short (5 days)- to long-term (4 months) corticosterone (CORT) administration by injection, pellet implantation, or in the drinking water decreased glial fibrillary acidic protein (GFAP) by 20-40% in hippocampus and cortex of intact rats. In contrast to CORT, adrenalectomy (ADX) caused elevations (50-125%) in hippocampus and cortex GFAP within 12 days of surgery that persisted for at least 4 months. CORT replacement of ADX rats decreased GFAP amount in hippocampus and cortex. The effects of long-term CORT and ADX on GFAP in hippocampus and cortex were also seen in striatum, midbrain, and cerebellum, findings suggestive of brain-wide adrenal steroid regulation of this astrocyte protein. The changes in GFAP amount due to CORT and ADX were paralleled by changes in GFAP mRNA, indicating a possible transcriptional or at least genomic effect of adrenal steroids. Glucocorticoid regulation of GFAP was relatively specific; it could not be generalized to other astrocyte proteins or other major structural proteins of neurons. The negative regulation of GFAP and GFAP mRNA by adrenal steroids suggested that increases in GFAP that result from brain injury may be attenuated by glucocorticoids. However, chronic CORT treatment of intact rats did not reverse or reduce the large increases in GFAP caused by trauma- or toxicant-induced brain damage. Thus, glucocorticoids and injury appear to regulate the expression of GFAP through different mechanisms. In contrast to the lack of effects of CORT on brain damage-induced increases in GFAP, CORT treatment begun in 2-week ADX rats, after an increase in GFAP had time to occur, did reverse the ADX-induced increase in GFAP. These results suggest that the increase in GFAP resulting from ADX is not mediated through an injury-linked mechanism.
TL;DR: Whether metabolism of CS occurs in the renal target cells of aldosterone, i.e. in cortical collecting duct cells, and if it does so, whether this activity is sufficient to reduce intracellular CS levels to allow binding of a Aldosterone to the mineralocorticoid receptor.
Abstract: Aldosterone selectivity in mineralocorticoid target tissues has been suggested to be due to 11β-hydroxysteroid dehydrogenase (11-OHSD), which, by inactivating the endogenous glucocorticoids cortisol and corticosterone (CS), would allow aldosterone to bind to the mineralocorticoid receptor that has equal affinity for aldosterone and natural glucocorticoids. However, a recent immunohistochemical study failed to colocalize 11-OHSD and mineralocorticoid receptors in the kidney. The goal of this study was to determine 1) whether metabolism of CS occurs in the renal target cells of aldosterone, i.e. in cortical collecting duct cells, and 2) if it does so, whether this activity is sufficient to reduce intracellular CS levels to allow binding of aldosterone to the mineralocorticoid receptor. Cortical collecting duct cells were isolated by solid phase immunoadsorption, with a cell purity of ∼98%. Metabolism of CS was studied in both freshly isolated cells and primary cultures grown as monolayers on permeable suppo...
TL;DR: Data demonstrate that activation of the HPAA by a subpyrogenic dose of LPS is macrophage dependent, however, Macrophage-independent mechanisms mediate activation ofThe HPAA in response to a pyrogenic doses of L PS.
Abstract: The mechanisms by which bacterial endotoxin [lipopolysaccharide (LPS)] stimulates the hypothalamo-pituitary- adrenal axis (HPAA) have not been elucidated. The present study was designed to investigate the involvement of macrophages in plasma ACTH and corticosterone responses to LPS administration in rats using selective in vivo macrophage depletion. Intraperitoneal administration of subpyrogenic doses of LPS to normal rats resulted in elevated plasma ACTH and corticosterone concentrations, measured 2 h later. The response showed a remarkable steep dose relationship, with minimal effective doses between 0.5-1.5 μg (ACTH) and 0.5 ng or less (corticosterone)μg BW. Plasma PRL, LH, and catecholamine (norepinephrine, epinephrine) levels were not significantly changed under the conditions used. Only at 6 h after LPS administration was a small elevation of norepinephrine noted. To deplete macrophages, rats were injected with liposomes encapsulated with dichloromethylene diphosphonate (Cl2MDP). Histochemical (acid...
TL;DR: The results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day, which strongly suggests that the facilitatory effects of chronic STz-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs.
Abstract: We have used streptozotocin (STZ)-induced diabetes in rats to determine whether this represents a sustained stimulus to the adrenocortical system and whether STZ-diabetic rats are able to mount an acute stress response. Furthermore, we compared pituitary responsiveness to CRF and/or arginine vasopressin, and adrenal responsiveness to ACTH in STZ- vs. vehicle-treated rats. We also compared the efficacy of dexamethasone inhibitory feedback in STZ-diabetic and control rats. Our results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day. Despite the evidence for sustained hypersecretion of B, STZ-treated rats showed greater and more prolonged ACTH and B responses to the acute stress of histamine injection. However, when tested separately, neither pituitary nor adrenal responsiveness to their secretagogues were increased in STZ-diabetic compared to control rats. Dexamethasone inhibition of stress-induced B secretion was tested using two different paradigms: pentobarbital-anesthetized rats were given iv injections of acid saline, and awake rats were given ip injections of histamine. In both experiments the STZ-treated rats were relatively resistant to glucocorticoid inhibition of stress responses. This finding, taken together with the exaggerated ACTH and B responses to stress, strongly suggests that the facilitatory effects of chronic STZ-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs, in conjunction with changes in glucocorticoid feedback sensitivity.
TL;DR: These studies imply that morphine-induced immunosuppression is at least in part mediated by the increase in serum corticosterone levels after implantation of the morphine pellet.
Abstract: Implantation of a 75-mg morphine pellet in sham-adrenalectomized male C3H/HeN mice resulted in significant elevations of serum corticosterone levels within 6 h Corticosterone levels remained elevated (3- to 4-fold) for 72 h and had returned to normal by 120 h postimplantation Within 48 h of pellet implantation, morphine-pelleted mice exhibited marked reductions in spleen (35%) and thymus weight (56%) relative to values in placebo-pelleted controls In addition, adrenal hypertrophy was observed in the morphine-pelleted shams (50% increase in adrenal weight relative to placebo) The magnitude of splenic and thymic atrophy was reduced by about 50% in adrenalectomized morphine-pelleted mice (17% and 22% reductions, respectively) compared to that in adrenalectomized mice implanted with placebo pellets Lymphocyte proliferative responses to the T-cell mitogen Concanavalin-A and the B-cell mitogen bacterial lipopolysaccharide were also significantly reduced in the morphine-pelleted sham mice Morphine-induced
TL;DR: Results from the present study strongly suggest a differential involvement of the hypothalamic noradrenergic innervation upon the hypothalamus-pituitary-adrenal axis according to the nature of stress conditions.
Abstract: The aim of the present study was to explore in male rats the role of the catecholaminergic innervation of the hypothalamus in corticotropic and adrenal responses to different kinds of stress conditions. For this purpose, 6-hydroxydopamine (3 μg in 0.2 μl saline) was stereotaxically and bilaterally infused at two levels of the main noradrenergic ascending brain stem bundle (NAB-X). The efficiency of catecholaminergic denervation of the hypothalamus was checked by measuring noradrenaline concentrations in paraventricular nuclei punches by HPLC and was confirmed by a 86% fall in noradrenaline levels of NAB-X rats killed after the stress experiments. Seven days after lesioning the NAB, sham operated controls and NAB-X lesioned animals were divided into 4 groups and submitted to 4 different stressors, i.e.: 2 min ether vapors (n = 5), 1 h immobilization (n = 7), i.v. histamine (2 mg/kg; n = 7) or i.v. insuline (10 I.U./kg; n = 8) injections. ACTH and corticosterone were measured in blood samples sequentially taken from a chronic carotid cannula, before stress and at short intervals over the 2 following hours. In comparison to the respective control groups, NAB-X dramatically reduced the ACTH response to ether (-78%) and to restraint (-53%) stress whereas the corticosterone response was affected to a lesser extent. In contrast, NAB-X slightly altered these responses in the histamine-treated group, although, surprisingly, the ACTH response tended to decrease and that of corticosterone to increase. Finally, NAB-X provoked a biphasic response to insulineinduced hypoglycemia, with a very early (5 min) rise in ACTH and corticosterone in comparison to the control group, followed by a trend to low hormonal levels up to 120 min. These results strongly suggest a differential involvement of the hypothalamic noradrenergic innervation upon the hypothalamic-pituitary-adrenal axis according to the nature of stress conditions.
TL;DR: Given that the Lewis rat has low basal levels of circulating corticosterone, and comparatively higher numbers of CD4-bearing lymphocytes, these factors may play a causative role in the known susceptibility of this strain to many experimental models of autoimmune disease.
TL;DR: There exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis.
Abstract: Differences in the regulation of type II glucocorticoid receptor (GR) mRNA levels in female rat brain regions involved in the control of the hypothalamic-pituitary-adrenal axis were studied by Northern blot analysis after chronic administration of corticosterone or dexamethasone to adrenalectomized (ADX), ovariectomized (OVX), and ADX/OVX animals. The effect of chronic estradiol or progesterone treatment of intact animals was also studied. Our results show that type II GR mRNA levels of ADX animals were significantly increased above control values in amygdala (140%) and hippocampus (196%), but not in hypothalamus. These increased transcript levels were down-regulated by corticosterone or dexamethasone, with the exception of those in the amygdala, where corticosterone had no effect. Ovariectomy significantly increased hypothalamic GR mRNA content (174%) over control values, and this increase was sensitive to dexamethasone. The combined effect of adrenalectomy/ovariectomy on GR mRNA levels was greater than that of adrenalectomy only in amygdala. Corticosterone increased amygdala transcript levels in OVX and ADX/OVX animals. Estradiol administration to intact animals raised the GR mRNA content of amygdala, while progesterone treatment had no effect on any of the brain regions studied. We conclude that there exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis. Our results also suggest that circulating estrogens can influence the sensitivity of brain structures (i.e. hypothalamus and amygdala) to glucocorticoids by altering GR mRNA levels. These regions may represent integration sites at which gonadal steroids are able to alter stress hormone secretion.
TL;DR: The activity and distribution of 11β-hydroxysteroid dehydrogenase in rat brain is described and highest enzyme activities were found in pituitary, cerebellum, hippocampus, and cortex, while lower levels are found in the olfactory region, hypothalamus, brain stem, preoptic nucleus, and amygdala.
Abstract: The activity and distribution of 11 beta-hydroxysteroid dehydrogenase in rat brain is described. Oxidation of corticosterone to 11-dehydrocorticosterone was significantly increased by NADP; the reverse reaction was increased by NADPH. Cortisol was a poor substrate. Both 11-dehydrogenase (11-DH) and 11-oxoreductase (11-OR) activities were found in brains of rats from 6 days to adult, and 11-DH and 11-OR activities were positively correlated with each other. Highest enzyme activities were found in pituitary, cerebellum, hippocampus, and cortex. Lower levels were found in the olfactory region, hypothalamus, brain stem, preoptic nucleus, and amygdala. Two antisera to 11-DH, designated 56-125 and 56-126, reacted with a 34K component corresponding in mass to rat liver 11-DH on Western blots. The dominant species of protein in all brain regions reacting with rat liver 11-DH antibody 56-125, was at 26K mol wt. Antiserum 56-126 did not cross-react with the 26K protein. The 26K component was not a 34K degradation product. In each region of the brain, Western blot analysis showed that the 26K band intensity was directly proportional to enzyme activity. However, the 26K protein was devoid of 11-DH activity. All 11-DH and 11-OR activities were associated with the 34K antigen. The data demonstrate the nonuniform distribution of 11-DH in brain tissue. They are consistent with the notion that 11-DH may confer upon brain the ability to control intracellular levels of active glucocorticoids and in this way mediate steroid function within the cell.
TL;DR: Results suggest that pulsatile secretion of corticosterone in rats has a primary periodicity near 60 min and is synchronized across animals, and the mechanism responsible for this synchronization is unknown.
Abstract: To establish whether adrenal corticosterone secretion is episodic and whether episodes are random or periodic events, adrenal extracellular fluid was sampled in awake rats by intra-adrenal microdialysis. Experiments conducted 1 or 2 days postsurgery between 1000 and 1830 h consisted of continuous collection of dialysate at intervals of 10 min. Pulses detected by PC-Pulsar had an interpulse interval of 54.1 +/- 4.5 and 51.3 +/- 5.0 min on days 1 and 2, respectively. Fourier analysis was used to determine whether significant periodicity was present. Six of seven of the day 1 animals had significant secretory rhythmicity, with a predominant periodicity at 60-80 min. In day 2 animals, in addition to a period near 50-80 min, a lower-frequency rhythm with a period near 213 min was identified. Autocorrelation analysis produced results qualitatively similar to Fourier analysis. Secretion rates were normalized based on maximal adrenal responses to adrenocorticotropic hormone and averaged at each time point. When the composite series was subjected to Fourier analysis, a significant rhythmicity (period 58 min) was still detectable in the day 1 animals. When composite data for the day 2 animals were analyzed, in addition to a component near 60-80 min, a lower frequency component near 320 min was present. The persistence of periodicity after time averaging suggests that corticosterone pulses are synchronized between animals. Cross-correlation analysis of individual pairs of data series supported synchronization in many cases. These results suggest that pulsatile secretion of corticosterone in rats has a primary periodicity near 60 min and is synchronized across animals. The mechanism responsible for this synchronization is unknown.