Showing papers on "Corticosterone published in 1985"
TL;DR: The hypothesis that cumulative exposure to corticosterone over the lifespan may contribute to age-related loss of neurons in the hippocampus is supported, and that prolonged stress or exposure to CORT accelerates this process of cell loss.
Abstract: The hippocampus of the rat loses neurons with age, a loss which may eventuate in some of the functional impairments typical of senescence Cumulative exposure to corticosterone (CORT) over the lifespan may be a cause of this neuronal loss, as it is prevented by adrenalectomy at mid- age In this study, we demonstrate that prolonged exposure to CORT accelerates the process of cell loss Rats were injected daily with sufficient CORT to produce prolonged elevations of circulating titers within the high physiological range Animals treated for 3 months (chronic subjects) resembled aged rats in a number of ways First, both groups had extensive and persistent depletions of CORT receptors in the hippocampus; in the case of chronic rats, no recovery of receptor concentrations occurred 4 months after the end of steroid treatment Second, autoradiographic analysis revealed that the receptor depletion was due, in part, to a loss of CORT-concentrating cells, especially in the CA3 cell field Remaining cells bound significantly less [3H]corticosterone than did those of control rats Finally, analysis of size distributions of hippocampal cell bodies indicated that chronic subjects lost neurons of the same size as those lost in the aged hippocampus Furthermore, chronic subjects also had increased numbers of small, darkly staining cells of CA3; these corresponded in size to the dark glia whose numbers increase in the aged hippocampus, and which are thought to infiltrate in response to neuronal damage or destruction Thus, this study supports the hypothesis that cumulative exposure to CORT over the lifespan may contribute to age-related loss of neurons in the hippocampus, and that prolonged stress or exposure to CORT accelerates this process
1,152 citations
TL;DR: It appears that corticosterone regulation of its own receptors emerges only by about the time of puberty, and that this permits an increase in receptor levels to occur despite the concurrently increasing levels of circulating cortic testosterone.
219 citations
TL;DR: It is concluded that there is a very narrow range of plasma corticosterone compatible with normal growth rate, thymus mass and ACTH secretion, which reveals the necessity for strict negative feedback regulation of ACTh secretion by corticosteroids.
Abstract: ACTH secretion appears to be under fairly tight negative feedback control by corticosteroids secreted from the adrenal cortex. In these studies we determined the circulating levels of a constant corticosterone signal that best restored body weight gain, thymus weight and ACTH levels to normal in bilaterally adrenalectomized rats given saline to drink. Young male rats were treated at the time of adrenalectomy with subcutaneously implanted pellets of wax or various ratios of corticosterone-cholesterol. Sham-adrenalectomized rats and adrenalectomized rats given corticosterone in the drinking fluid served as comparison groups. Rats were killed 3, 7, or 14 days after adrenalectomy. There was no difference in levels of plasma corticosterone in the morning and in the evening in pellet-implanted rats in contrast to the diurnal variation in the reference groups. Circulating corticosterone levels that best restored body weight, thymus weight, and resting and stress-induced ACTH levels to normal ranged between 4.5 and 7.4 micrograms/dl. Plasma corticosterone levels of 8-11 micrograms/dl were excessive and levels of 2-4 micrograms/dl were not adequate. We conclude that there is a very narrow range of plasma corticosterone compatible with normal growth rate, thymus mass and ACTH secretion. These results reveal the necessity for strict negative feedback regulation of ACTH secretion by corticosteroids.
198 citations
TL;DR: Evidence is presented for CORT compromising the capacity of hippocampal neurons to survive a variety of toxic insults, and the time-course of this effect suggests the relatively rapid metabolic actions of CORT as critical to this endangerment.
192 citations
TL;DR: The data specifically implicate the hippocampus in modulating feedback sensitivity, as down-regulation was extensive in this structure, and did not occur in the septum, amygdala, hypothalamus or pituitary.
166 citations
TL;DR: The data raise the possibility that the atrial natriuretic peptides may affect sodium excretion by the kidney, not only directly, but also indirectly through the inhibition of aldosterone production.
Abstract: This study examines the effects of the synthetic atrial peptides (atriopeptin I, II, and III) on aldosterone and corticosterone production by rat adrenal cell suspensions. Furthermore, we studied the effect of atriopeptin II infusion on the plasma aldosterone response to angiotensin II in the rat in vivo. Atriopeptin I, II, and III decreased aldosterone release from zona glomerulosa cells in a dose-dependent fashion. 10 pM atriopeptin II inhibited basal aldosterone release significantly (P less than 0.01), and 10 nM atriopeptin II or III lowered it by 79%. Atriopeptin II decreased the sensitivity of the glomerulosa cells to adrenocorticotropic hormone (ACTH) and angiotensin II. Atriopeptin II had no effect on basal or ACTH-stimulated corticosterone release by fasciculata-medullary cells. In vivo infusions of angiotensin II with or without simultaneous infusions of atriopeptin II showed that atriopeptin II significantly inhibited the aldosterone response to angiotensin II. This inhibition by atriopeptin II was independent of any effect on plasma renin activity, serum potassium, or ACTH. These data raise the possibility that the atrial natriuretic peptides may affect sodium excretion by the kidney, not only directly, but also indirectly through the inhibition of aldosterone production.
151 citations
TL;DR: Examination of the effects of postnatal handling of rat pups from Days 1 to 21 on the development of the intracellular, glucocorticoid receptor in the hippocampus, and pituitary transcortin, and corticoid binding globulin in plasma suggests a more efficient adrenocortical negative-feedback system in the handled animals.
Abstract: We have examined the effects of postnatal handling of rat pups from Days 1 to 21 on the development of the intracellular, glucocorticoid receptor in the hippocampus, and pituitary transcortin, and corticoid binding globulin in plasma. All animals were sacrificed 10-14h following adrenalectomy and the in vitro receptor assays were performed using 3H dexamethasone (intracellular receptors) or [3H] corticosterone (transcortin and corticoid binding globulin). Early handling resulted in a 30-40% increase in 3H dexamethasone binding (increase in Bmax with no change in Kd) in the hippocampus. In the pituitary handling was associated with a decrease in transcortin binding. There was no effect on plasma corticoid binding globulin. When tested as adults, nonhandled animals hypersecreted corticosterone following the termination of a stressor. This suggests a more efficient adrenocortical negative-feedback system in the handled animals and these data are consistent with previous work on the relationship between hippocampal glucocorticoid receptors and adrenocortical stress recovery.
143 citations
TL;DR: Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocor‐ticoids were given, and oestrogen replacement alone induced a pubertal growth spurt.
Abstract: Two siblings, a 9-week-old female and an 18-year-old male pseudohermaphrodite are described with deficient cholesterol side-chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycorticosterone and corticosterone were unmeasurable. Urinary 17-hydroxycorticosteroids (17-OHCS), tetrahydrocortisol, 17-ketosteroids (17-KS), pregnanetriol, pregnanediol, and delta 5-3 beta-ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radiolabelled cholesterol to pregnenolone. The gluccocorticoid and mineralocorticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocorticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long-term steroid replacement therapy, and comparison with previously reported findings are discussed.
138 citations
TL;DR: The hypothesis that in this amphibian, exposure to acute stress or to exogenous corticosterone can suppress plasma androgen titers by inhibiting the release of LH-RH from the hypothalamus is supported.
137 citations
TL;DR: Evidence for the existence of specific glucocorticoid receptors in the rat frontal cortex is presented, providing a possible mechanism for the influence of corticoids on catecholamine activity in the frontal cortex.
137 citations
TL;DR: The data are interpreted as suggesting that glucocorticoid secretion under basal conditions and during stress may differentially effect specific brain structures in male vs female rats.
TL;DR: The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans.
Abstract: Aldosterone binding sites in human mononuclear leukocytes were characterized after separation of cells from blood by a Percoll gradient. After washing and resuspension in RPMI-1640 medium, cells were incubated at 37 degrees C for 1 h with different concentrations of [3H]aldosterone plus a 100-fold concentration of RU-26988 (11 alpha, 17 alpha-dihydroxy-17 beta-propynylandrost-1,4,6-trien-3-one), with or without an excess of unlabeled aldosterone. Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM (means +/- SD, n = 14) and a capacity of 290 +/- 108 sites/cell (n = 14). The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone. The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans.
TL;DR: A six-month-old 46,XY infant with a female phenotype and ambiguous genitalia was evaluated for male pseudohermaphroditism, and the unusual pattern of plasma and urinary steroids indicated that this child had multiple abnormalities of steroid-biosynthetic microsomal mixed-function oxidases--21-hydroxylase, 17 alpha-hydrogenase, and 17,20 desmolase.
Abstract: A six-month-old 46,XY infant with a female phenotype and ambiguous genitalia was evaluated for male pseudohermaphroditism. The principal findings were (1) low basal plasma levels of all measured C19 steroids and their sulfates, which were unchanged or only minimally increased after stimulation with human chorionic gonadotropin or ACTH, (2) no urinary metabolites of C19 11-deoxy steroids, and decreased amounts of C19 11-oxo steroids, (3) normal basal plasma cortisol levels and normal urinary excretion of cortisol metabolites, (4) high plasma corticosterone and deoxycorticosterone levels and elevated urinary excretion of their metabolites, (5) high plasma progesterone and pregnenolone levels and increased urinary excretion of pregnanediol and pregnenediol, (6) high plasma 17α-hydroxyprogesterone and 21-deoxycortisol levels and increased urinary excretion of pregnanetriol, 17α-hydroxypregnanolone, and pregnenetriolone, (7) high plasma and urinary levels of 5-pregnene-3β,20α-diol sulfate, (8) low pla...
TL;DR: The effect on emotional reactivity produced by a model for chronic stress in which different types of acute stresses were randomly combined for 29 days was studied in adult male rats, showing a slight decrease in body weight gain and an increase in relative adrenal weight.
TL;DR: The results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.
Abstract: The blood-brain barrier restricts the passage of molecules from the blood to the brain. The permeability of the barrier to iodine-125-labeled bovine serum albumin was examined in rats that had undergone adrenalectomy, adrenal demedullation, and corticosterone replacement. Adrenalectomy, but not adrenal demedullation, increased the permeability of brain tissue to the isotopically labeled macromolecule; corticosterone replacement reversed this effect. These results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.
TL;DR: Lesion rats demonstrated a behavioral deficit in food intake regulation in response to 5-hr and 24-hr fasts, showed a disturbance in circadian feeding, and exhibited a dramatic decrease in circulating corticosterone, suggesting that noradrenergic receptors within the PVN are not involved in the mediation of glucoprivic-induced feeding.
TL;DR: It is demonstrated that corticosterone and the related glucocorticoid, dexamethasone, induce different anatomical patterns of 'down-regulation', which appear due to differential access of the two steroids to the receptor pools.
Journal Article•
TL;DR: It is concluded that GIF has no direct action on the adrenals in vivo and that a functional pituitary gland is essential for its action, and the existence of a glucocorticoid associated immunoregulatory feedback circuit is suggested.
Abstract: Products are released in vitro by mitogen stimulation of human peripheral blood mononuclear cells or rat spleen cells which increase corticosterone blood levels when injected into normal rats. We report that an almost pure population of human peripheral blood lymphocytes in mixed lymphocyte culture stimulated with phytohaemagglutinin also produces a glucocorticoid increasing factor(s). The product equivalent to the amount released by 5 X 10(5) cells increased corticosterone levels four-fold and also increased ACTH levels. When rats were hypophysectomized or treated with dexamethasone to block ACTH output, no corticosterone increase was noted following administration of glucocorticoid increasing factor(s) (GIF). Similar results were obtained with supernatants of rat spleen cells stimulated with concanavalin A. We conclude that GIF has no direct action on the adrenals in vivo and that a functional pituitary gland is essential for its action. The presented data taken together with those described earlier suggest the existence of a glucocorticoid associated immunoregulatory feedback circuit.
TL;DR: It is concluded that intact adrenocortical secretion of glucocorticoids is sufficient for retention of acquired immobility during forced swimming.
TL;DR: The data indicate that atriopeptins are potent and specific inhibitors of aldosterone synthesis in cells prepared from the zona fasciculata and that the Phe-Arg-Tyr carboxy-terminal extension of atriopes altered basal ald testosterone release.
Abstract: The effect of synthetic atriopeptins on basal and stimulated aldosterone secretion was determined in isolated adrenal glomerulosa cells of the rat. Neither atriopeptin I (1-21) or III (1-24, i.e., the Phe-Arg-Tyr carboxy-terminal extension of atriopeptin I) altered basal aldosterone release. However, if the cells were prepared from adrenals of sodium-depleted rats, the basal aldosterone release was increased by 9-fold, compared with cells from normal rats. This elevated release was inhibited by 32% by atriopeptin I and atriopeptin III. Atriopeptin III was more potent than atriopeptin I. Angiotensin II and adrenocorticotropin stimulated the release of aldosterone in a concentration-related manner. Both atriopeptin I and atriopeptin III inhibited the stimulation by the peptides. Atriopeptin I inhibited angiotensin II- and adrenocorticotropin-induced aldosterone production by 50% at concentrations of 12 and 11 nM, respectively, and 0.5 and 0.2 nM, respectively, for atriopeptin III. Potassium-stimulated aldosterone production was also inhibited by atriopeptin I and atriopeptin III with 50% inhibition at concentrations of 10 and 0.4 nM, respectively. Shorter peptides (1-20, 1-19, and 3-19) were equipotent to atriopeptin I (1-21) as inhibitors of angiotensin II-induced steroidogenesis. To determine the site at which atriopeptins inhibit aldosterone synthesis, we used cyanoketone to inhibit 3 beta-hydroxy-dehydrogenase and dissociate the early and late pathways. Angiotensin II (2 nM) increased the synthesis of pregnenolone (early pathway), as well as the conversion of [3H]corticosterone to [3H]aldosterone (late pathway). Atriopeptin III inhibited basal pregnenolone synthesis by 36% and completely blocked angiotensin II-stimulated synthesis. The peptide similarly inhibited the late pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results demonstrate that after short term stress the septo-hippocampal cholinergic system is activated secondary to activation of the pituitary-adrenocortical axis and major changes in circulating corticosterone can modulate the activity of the hippocampalCholinergic synapse.
TL;DR: The preliminary data lend support to the view that an increased pituitary ACTH reserve or adrenocortical steroid reserve is not likely to be responsible for the defective pituitsary-adrenal regulation in some dexamethasone-resistant depressives.
TL;DR: The results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid‐synthetic pathway (e.g. cholesterol‐side‐chain cleavage enzyme) is of little clinical relevance.
Abstract: In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.
TL;DR: The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on neurotransmitter receptors was studied in dorsal hippocampus of rat using quantitative autoradiography.
TL;DR: There is no autonomous response of the corticotrope to ADX; the removal of corticosterone from the anterior pituitary may account for the majority of the effects of ADX on ACTH synthesis; and the normal response toADX requires secretion of CRF and increased secretion of another ACTH-releasing factor (possibly arginine vasopressin) that causes increased secretion but little synthesis of ACTH.
Abstract: In the intact rat, adrenalectomy (ADX) is known to result in increased ACTH synthesis, content, and secretion from the anterior pituitary compared with those in the shamadrenalectomized control. Treatment of adrenalectomized, rats with corticosterone prevents or reverses these changes in ACTH. Because corticosterone is known to act both at the corticotrope and at the level of CRF secretion, it is not clear to what extent the ACTH response to ADX is a result of removal of glucocorticoids from the pituitary per se. To test the role of brain input as well as the role of glucocorticoids on the corticotrope response to ADX, we performed the following experiment. Rats were prepared with anterolateral hypothalamic deafferentations (lesion) which severed CRF and arginine vasopressin cell bodies in the hypothalamus from their axonal endings in the median eminence and posterior pituitary. Control rats were subjected to sham lesions. Two days later, half of the rats in each group were subjected to either ADX or sham...
TL;DR: Stress-induced tumor growth, associated with inoculation with fetal rats cells transformed by tumor virus, is accelerated in aged rats and simulation of the aged pattern of corticosterone hypersecretion in young animals using steroid administration similarly accelerates stress- induced tumor growth.
Abstract: Aged males rats show a delay in terminating their adrenocortical stress response and, thus, hypersecrete corticosterone during the poststress period. Because of the numerous catabolic effects of corticosterone, we hypothesized that chronic stress should induce greater pathophysiological changes in aged than in young subjects. We report that stress–induced tumor growth, associated with inoculation with fetal rats cells transformed by tumor virus, is accelerated in aged rats. Furthermore, simulation of the aged pattern of corticosterone hypersecretion in young animals using steroid administration similarly accelerates stress–induced tumor growth. (Endocrinology 117: 662–666, 1985)
TL;DR: The results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of thepituitaries, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids.
Abstract: The effect of the continuous exposure to ovine corticotropin-releasing factor (oCRF) was measured in adult male rats. The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values. Additionally, corticotropin-releasing factor (CRF)-treated rats had decreased plasma testosterone levels. The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content. In these animals, CRF markedly inhibited luteinizing hormone (LH) (but not follicle-stimulating hormone [FSH] ), testosterone, and PRL secretion and decreased seminal vesicle weights. All the effects of CRF were mimicked by exogenously administered ACTH. By contrast, with the exception of FSH secretion, which was slightly elevated by CRF, neither CRF nor ACTH were able to significantly modify reproductive parameters in adrenalectomized animals, which suggests that the elevation of circulating levels of adrenal steroids induced by peripherally administered CRF represents major mediators of CRF-induced inhibition of fertility. These results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of the pituitary-adrenal axis, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids. The increased secretion of adrenal steroids by CRF-treated rats is believed to participate in the disruption of reproductive parameters observed in these rats.
TL;DR: Comparisons between the selected lines and various crosses showed additive and nonadditive genetic variation but no maternal effects for response to social stressors as measured by heterophil/lymphocyte ratios.
TL;DR: The results suggest that conversion of corticosterone and of 18-hydroxycorticosterone to aldosterone occurs through P-45011 beta-catalyzed reaction.
Abstract: When corticosterone was incubated with cytochrome P-45011 beta purified from bovine adrenocortical mitochondria in the presence of adrenodoxin, NADPH-adrenodoxin reductase and an NADPH generating system, aldosterone as well as 18-hydroxycorticosterone were formed with turnover numbers of 0.23 and 1.1 nmol/min/nmol P-450, respectively. Phospholipids extracted from adrenocortical mitochondria remarkably enhanced the activity of aldosterone formation by the cytochrome P-45011 beta-reconstituted system. The apparent Km and turnover number were estimated to be 6.9 microM and 2.0 nmol/min/nmol P-450 for aldosterone formation in the presence of the lipidic extract. When 18-hydroxycorticosterone was tested as a substrate, cytochrome P-45011 beta showed catalytic activity for aldosterone synthesis with an apparent Km and turnover number of 325 microM and 5.3 nmol/min/nmol P-450, respectively. Carbon monoxide and metyrapone inhibited the production of aldosterone from corticosterone and that from 18-hydroxycorticosterone. These results suggest that conversion of corticosterone and of 18-hydroxycorticosterone to aldosterone occurs through P-45011 beta-catalyzed reaction.
TL;DR: The results of the experiments suggest that the effect of fenfluramine on prolactin secretion is mediated, at least in part, by a serotoninergic mechanism, but the effect on corticosterone secretion is not mediated via serotonin release.
Abstract: Administration of the serotonin-releasing drug fenfluramine to male rats caused a dose-dependent increase in both plasma prolactin and corticosterone levels. The effect of fenfluramine on prolactin wa