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Showing papers on "Corticosterone published in 1976"


Journal ArticleDOI
TL;DR: The normal values for the excretory ratio of the major urniary metabolites of these two steroids are presented to provide a basis for the diagnosis of abnormalities in their ratio.
Abstract: The abnormal steroid pattern in an inborn error in aldosterone biosynthesis consists of overproduction of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone. The normal values for the excretory ratio of the major umiary metabolites of these two steroids are presented to provide a basis for the diagnosis of abnormalities in their ratio. The production of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone is remarkably constant over a large range of absolute values, except in the disorder involving the terminal portion of the aldosterone biosynthetic pathway for which the term corticosterone methyl oxidase defect, Type 2, is suggested.

203 citations


Journal ArticleDOI
R.J. Etches1
01 Dec 1976-Steroids
TL;DR: Tests of adrenal function showed that stimulation of the adrenal with exogenous ACTH and with dexamethasone caused an increase and decrease, respectively, in plasma concentrations of corticosterone.

185 citations


Journal ArticleDOI
TL;DR: The pattern of in vivo labeling by [3H]corticosterone and [3h]dexamethasone differs from the in vivo distribution of [3 H]estradiol in ADX-OVX rats using the same dissection procedure and this demonstrates the regional differentiation within brain of steroid hormone uptake and 'receptor' processes.

137 citations


Journal ArticleDOI
TL;DR: An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level and the pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response.
Abstract: An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level. Rats were injected with cyclophosphamide 30 min after consuming a novel saccharin drinking solution. Plasma corticosterone levels were measured before conditioning to determine unconditioned steroid levels and 3 and 6 days after training when conditioned and nonconditioned animals were provided with the saccharin solution or plain water, or were left deprived. The pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response. There were no differences between the steroid levels of conditioned and nonconditioned animals supplied with plain water or those that remained deprived, although deprivation increased corticosterone levels. Nonconditioned rats presented with saccharin had steroid levels that did not differ from control values. Conditioned animals presented with saccharin showed an elevation in steroid level which was significantly greater than that observed in any other group. Comparable results were obtained when LiCl was used as the unconditioned stimulus.

132 citations


Journal ArticleDOI
TL;DR: The results indicate that glucocorticoids have a significant role in the regulation of brain tryptophan hydroxylase: possibly as an inducing signal during neonatal development and as a permissive factor at adult age.
Abstract: —The normal developmental rise of tryptophan hydroxylase levels in neonatal rat brain was blocked by adrenalectomy. Similarly, adrenalectomy prevented the rescrpine-induced elevation of tryptophan hydroxylase activity in brain stem of adult mice. In both cases, the effects of adrenalectomy could be reversed by replacement injections of corticosterone. Repeated injections of corticosterone (5 mg/kg daily) in fact induced a rise of brain tryptophan hydroxylase levels in neonatal brain. However, neither adrenalectomy nor repeated injections of large doses of the hormone (20 mg/kg, daily) was found to be effective in affecting the normal enzyme levels in adult brain. Apparent Km of the enzyme for substrate was unchanged by corticosterone in vivo or in vitro. These results indicate that glucocorticoids have a significant role in the regulation of brain tryptophan hydroxylase: possibly as an inducing signal during neonatal development and as a permissive factor at adult age.

127 citations


Journal ArticleDOI
TL;DR: Female rats were subjected to 8 h of daily immobilization for 1, 3, 6, 10 or 15 days to induce adrenal enlargement as well as thymus involution in response to stress.
Abstract: Female rats were subjected to 8 h of daily immobilization for 1, 3, 6, 10 or 15 days. Exposure for 3 days inhibited b.w. and induced adrenal enlargement as well as thymus involution; 6 days of stress

115 citations


Journal ArticleDOI
TL;DR: In an attempt to interfere with the normal glucocorticoid binding of the hippocampus as well as with the postadrenalectomy increase of the cytosol binding sites, bilateral transection of the fimbria was performed either 3 days or 80 days before ADX.

101 citations


Journal ArticleDOI
TL;DR: The binding of [ 3H]corticosterone and [3H] dexamethasone to soluble macromolecules in the pituitaries of adrenalectomized rats perfused at sacrifice to remove blood contamination is described.

101 citations


Book ChapterDOI
01 Jan 1976
TL;DR: In this paper, the effect of varying time intervals of acute IMO on CA concentration in the hypothalamus and on plasma ACTH and B levels has been studied, by relating the changes to the duration of stress.
Abstract: Publisher Summary Evidence indicating the participation of hypothalamic catecholamines (CA) in neuroendocrine processes, particularly in regulating the secretion of releasing and inhibiting hormones or factors in the hypothalamus, has been reported. These neuroendocrine reactions are activated under stress. The present study aims to determine whether CA undergoes any changes in individual regions of the hypothalamus (HPT) in stressed rats, and to study the correlation of these changes with the alterations of typical indicators of stress-levels of plasma adrenocorticotropic hormone (ACTH) and corticosterone (B). The present experiments were conducted to elucidate the dynamics of CA changes in the HPT, by relating the changes to the duration of stress. Immobilization (IMO) was used as the model of stress. The effect of varying time intervals of acute IMO on CA concentration in the HPT and on plasma ACTH and B levels has been studied.

96 citations


Journal ArticleDOI
TL;DR: The strain specific steroidogenic patterns, characterized by the relative magnitudes of 18- and 11beta-hydroxylase activities, were found to be determined by adrenal mitochondrial cytochrome P-450 particles, and data strongly suggest the same cyto Chrome is involved in both 18-and- 11 beta hydroxylation and that this cy tochrome is mutated between S and R rats.
Abstract: A reciprocal relationship between steroid 18- and 11beta-hydroxylase activities in the salt susceptible (S) and the salt resistant (R) strains of rats was previously shown to be controlled by a single genetic locus with two alleles and inheritance by co-dominance (Rapp, J. P., and Dahl, L. K. (1972), Endocrinology 90, 1435). The strain specific steroidogenic patterns, characterized by the relative magnitudes of 18- and 11beta-hydroxylase activities, were found to be determined by adrenal mitochondrial cytochrome P-450 particles. Carbon monoxide inhibition of 18- and 11beta-hydroxylation of deoxycorticosterone in these strains showed that the CO/O2 ratio causing 50% inhibition (i.e., Warburg's partition constant, K) was identical for 18- and 11beta-hydroxylation within a strain, but different for both 18- and 11 beta hydroxylation between strains. (K values were: S rats, 18-hydroxylation = 11.4 +/- 1.4; S rats, 11beta-hydroxylation = 11.0 +/- 1.2; R rats, 18-hydroxylation = 56.4 +/- 13.7; R rats, 11beta-hydroxylation = 46.7 +/- 11.7). This between-strain difference was unique for 18- and 11beta-hydroxylation; i.e., it was not seen with cholesterol side-chain cleavage or 21-hydroxylation. Moreover, the strain-specific K values for 18- and 11beta-hydroxylase and the strain-specific steroidogenic patterns due to the relative magnitudes of 18- and 11beta-hydroxylase activities segregated together in an F2 population. These data strongly suggest the same cytochrome P-450 is involved in both 18- and 11beta-hydroxylation and that this cytochrome is mutated between S and R rats. K values for the reaction corticosterone leads to 18-hydroxycorticosterone were different between S and R strains, indicating that the mutant cytochrome was also involved in this hydroxylation, but K values for the conversion corticosterone leads to aldosterone were not different between strains. This was interpreted to mean that each step in the sequence corticosterone leads to 18-hydroxycorticosterone leads to aldosterone was mediated by a different cytochrome, the K value for the second step being the lower and dominating the overall reaction. It was speculated that the second step could be a second hydroxylation at position 18 to yield 18,18-dihydroxycorticosterone which could be unstable and decompose into aldosterone and water.

96 citations


Journal ArticleDOI
TL;DR: Findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.
Abstract: The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adreanl at 12 h resulted in an enlarged right adrenal at 12h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement at 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.

Journal ArticleDOI
TL;DR: Lesions in the VMN and DMN, both of which have previously been shown to disrupt normal diurnal feeding rhythms, were also observed to disruptnormal plasma corticosterone rhythms in the present study.
Abstract: Weanling rats received bilateral electrolytic lesions in the dorsomedial (DMH) or ventromedial (VMH) hypothalamic areas destroying primarily the dorsomedial (DMN) or ventromedial (VMN) hypothalamic nuclei. Sham-operated rats served as controls. Lesions in the VMN and DMN, both of which have previously been shown to disrupt normal diurnal feeding rhythms, were also observed to disrupt normal plasma corticosterone rhythms in the present study. The a.m. values of plasma corticosterone in the DMN-lesioned rats were higher than the sham-operated controls. In the p.m., the values of both VMN- and DMN-lesioned rats were lower than those of the controls but unchanged in comparison to their own a.m. concentrations. This disruption of the normal diurnal plasma corticosterone rhythm persisted for at least 9 post-operative weeks.

Journal ArticleDOI
TL;DR: Observations similar to those on rats 15,t7,24 are made by cell fractionation and nuclear isolation (NI) as well as by radioautography (RA), of differential binding and retention of radioactivity from estrogens and glucocorticoids by cells in particular regions of the brain and pituitary.

Journal ArticleDOI
TL;DR: The hypothesis that a serotonin neural pathway stimulates ACTH secretion in rats was supported by pharmacologic data and the dose-response characteristics for corticosterone elevation and L-5HTP potentiation by fluoxetine were similar to those for serotonin uptake blockade.

Journal ArticleDOI
Hilfenhaus M1
TL;DR: The renin-angiotensin-aldosterone system of the rat is subject to a circadian rhythm which is largely in phase with the well-known rhythm of the pituitary-adrenal axis, and the finding that PAC and PCC follow the same pattern of circadian variations under every experimental condition tested is suggested.
Abstract: The 24 h-course of plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma corticosterone concentration (PCC) and of the urinary excretion of sodium, potassium and aldosterone was investigated in male Sprague-Dawley rats under different experimental conditions. The data obtained can be summarized as follows: 1. The renin-angiotensin-aldosterone system (RAAS) of the rat is subject to a circadian rhythm which is largely in phase with the well-known rhythm of the pituitary-adrenal axis. This rhythm can be demonstrated in PRA as well as in plasma concentrations and urinary excretion rates of aldosterone. The rhythm of urinary excretion of electrolytes is unlikely to be due to the rhythm of aldosterone secretion. 2. The light-dark cycle is the main synchronizer for these rhythms: inverting the light-dark cycle for 5 weeks entirely inverts the rhythms of all the parameters cited. 3. A dissociation of the rhythms of PRA and PAC can be observed following sodium restriction or dexamethasone treatment. A role of ACTH IN regulating the rhythmic pattern of aldosterone secretion is suggested by the finding that PAC and PCC follow the same pattern of circadian variations under every experimental condition tested. 4. The responsiveness of the RAAS to stimulation or suppression varies with the time of day. 5. It is suggested that experiments ought to be performed not only during the inactive (light hours) but also during the active (dark hours) phase when investigating the RAAS in the rat. This can conveniently be achieved by the use of an animal room with a reversed lighting regime.

Journal ArticleDOI
TL;DR: The results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.
Abstract: 1. Isolated hind limbs of rats were perfused and vascular smooth muscle sensitivity to noradrenaline, methoxamine and potassium chloride was measured and dose-response curves were obtained. 2. The sensitivity of vascular smooth muscle to noradrenaline is attenuated by adrenalectomy and low sodium diet; it is enhanced by corticosterone. High sodium diet or administration of deoxycorticosterone did not alter the dose—response curve significantly. 3. The increased sensitivity of vascular smooth muscle after corticosterone treatment is not related to changes in the contractile protein or alterations in the neuronal uptake and extraneuronal metabolism of noradrenaline. 4. These results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.

Journal ArticleDOI
TL;DR: The influence of the hippocampus upon pituitary release of adrenocorticotropic hormone (ACTH) was studied in male Sprague-Dawley rats which had concentric bipolar stainless stell electrodes chemically implanted in the dorsal and ventral hippocampus.
Abstract: The influence of the hippocampus upon pituitary release of adrenocorticotropic hormone (ACTH) was studied in male Sprague-Dawley rats which had concentric bipolar stainless steel electrodes chronicall

Journal ArticleDOI
TL;DR: Early after induction of diabetes there is adrenal hyperfunction of the mixed type (i.e. gluco and mineralcorticoid), and that in the later periods (2-3 months), the deranged metabolism of the diabetic rat acts as a chronic stress.
Abstract: Male Wistar rats were treated with an i.v. dose of 100 mg/kg of Streptozotocin (STZ). Either 5 days or 1, 2 or 3 months after induction of diabetes, the adrenal function of these animals was studied. Short course diabetes (5 days) was accompanied by adrenal hypertrophy and high plasma corticosterone levels; during later periods the diabetic rats consistently showed signs of adrenal hyperactivity, yet both adrenal weight and plasma corticosterone tended to be lower than in the 5 day-treated animals. Adrenal incubations with 14C-progesterone showed that 5 days and one month diabetic animals synthesized more deoxycorticosterone than controls; production of corticosterone and 18-hydroxydeoxycorticosterone was normal at all time periods studied. Synthesis of 18-hydroxycorticosterone, a compound which affects sodium metabolism, was increased in 5 day-treated rats; thereafter, the function of the zona glomerulosa seemed to be impaired in diabetic rats. These results suggest that early after induction of diabetes there is adrenal hyperfunction of the mixed type (i.e. gluco and mineralcorticoid), and that in the later periods (2-3 months), the deranged metabolism of the diabetic rat acts as a chronic stress.

Journal ArticleDOI
TL;DR: It is suggested that corticosterone is the critical hormone of the pituitary-adrenal axis in the control of avoidance responding in agonistic situations and ACTH and cortic testosterone affect avoidance-of-attack differently from the way they have been shown to affect avoidance responses in shock-mediated situations.

Journal ArticleDOI
TL;DR: Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycORTicosterone contribute little to receptor occupancy.
Abstract: Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.

Journal ArticleDOI
TL;DR: In contrast to its effect in cortisol-producing animals, the administration of spironolactone caused an increase in the activities of the microsomal 21-hydroxylases in the adrenals of corticosterone- producing animals such as the rat and the rabbit.

Journal ArticleDOI
TL;DR: The postnatal development of adrenocortical function was determined in C57BL/10 and DBA/1 mice by CPB assay of basal and stressinduced levels of plasma corticosterone and resting levels of brain Corticosterone, and the developmental change in brain cortic testosterone was similar to the pattern found in plasma.
Abstract: A competitive protein-binding (CPB) assay, suitable for measuring corticosterone levels in 20 (μl of mouse plasma or 100 mg of brain, is described. The postnatal development of adrenocortical function was determined in C57BL/10 and DBA/1 mice by CPB assay of basal and stressinduced levels of plasma corticosterone and resting levels of brain corticosterone. Marked increases in both basal and stressed levels of plasma corticosterone were found beginning at day 12 after birth: mean basal levels rose from about 1 /μg/100 ml on day 12 to peak values of about 10–15 /μg/100 ml on days 18–20, and then declined by day 30 to the 13-day level of 2.6 /μg/100 ml. This pattern differs significantly from results obtained with standard fluorometric assays for corticosterone; it was determined that a major part of this discrepancy is due to the lack of specificity of the fluorometric assay. The developmental change in brain corticosterone was similar to the pattern found in plasma. Only the stress-induced levels of plasma...

Journal ArticleDOI
TL;DR: It is proposed that both enzymic functions are functionally related and may involve the same enzyme protein and catalytic site of the fasciculata zone and 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) does not meet these criteria and, although its overproduction in unselected low renin essential hypertensive patients remains controversial, the magnitude of the reported elevations is insufficient in relation to the low biologic activity of the steroid.
Abstract: Low renin essential hypertension and the syndrome of mineralocorticoid excess have two features in common, low plasma renin activity and volume-sensitive hypertension. The proposal that both disorders share a common mechanism--because of the ability of agents that inhibit or antagonize the adrenocortical secretion to lower blood pressure in the low renin hypertensive group--appears to be based on a circular argument. The beneficial effect of removal or neutralization of the adrenocortical contribution only constitutes evidence for volume-dependency or sensitivity, which is how the low renin group is defined. Any measure that blocks a component of the normal homeostatic chain for the maintenance of extracellular and intravascular volume including the adrenal cortex would be expected to have a beneficial effect in volume-sensitive hypertension. Evidence for an adrenal factor in low renin hypertension must rest on the isolation of an active substance that reproduces the effect when readministered. 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) does not meet these criteria. It is not significantly increased in experimental hypertension and, although its overproduction in unselected low renin essential hypertensive patients remains controversial, the magnitude of the reported elevations is insufficient in relation to the low biologic activity of the steroid to account for a significant effect. Apart from its increase in the 17alpha-hydroxylase defect, 18-OH-DOC is increased in primary aldosteronism and may also be an indicator of a histologic variant of the aldosteronoma. On the basis of a large body of evidence showing parallelism between the 11beta- and 18-hydroxylase functions of the fasciculata zone, we have proposed that both enzymic functions are functionally related and may involve the same enzyme protein and catalytic site. According to this view, the secretion of 18-OH-DOC would have no special significance of its own but would be an obligatory consequence of the secretion of fasciculata zone corticosterone.

Journal ArticleDOI
TL;DR: Structural-activity studies showed that different steroids have different effects on both fast and delayed feedback at the hypothalamus, and suggested that the mechanism of action of the fast feedback of corticosteroids is via membrane stabilization.

Journal ArticleDOI
TL;DR: The action of corticosterone on active avoidance behaviour is mediated, at least in part, via changed 5-HT metabolism in the brain, as correlated with hypothalamic and mesencephalic serotonin (5-HT) content.

Journal ArticleDOI
TL;DR: The present studies were undertaken to determine if corticosterone levels are elevated in acidotic rats and if so, whether acidosis stimulates the adrenal glands directly or via the pituitary-adrenal axis.
Abstract: Previous studies have demonstrated that the adrenal glands were necessary for acidosis activation of the mitochondrial glutaminase I pathway. The present studies were undertaken to determine if corticosterone levels are elevated in acidotic rats and if so, whether acidosis stimulates the adrenal glands directly or via the pituitary-adrenal axis. Metabolic acidosis induced by NH4Cl, either acute or chronic, increased corticosterone levels 100 to 130% in intact rats. Acute metabolic acidosis did not activate the mitochondrial pathway in adrenalectomized rats; corticosterone levels were not elevated in hypophysectomized rats nor did activation of the mitochondrial pathway occur in response to acidosis. Therefore, acidosis does not stimulate the adrenal gland directly; rather, it requires the intact pituitary. Administering exogenous corticotropin to hypophysectomized rats resulted in elevation of plasma corticosterone levels and activation of the mitochondrial pathway. The pituitary-adrenal cortex-renal glut...

Journal ArticleDOI
TL;DR: Rats exposed to 1 of 4 treatments related to the extinction of appetitive operant behavior yielded unchanged steroid levels in the absence of food, but significantly suppressed plasma corticosterone when food continued to be delivered.

Journal ArticleDOI
TL;DR: The results indicate that the autonomous capacity of foetal adrenals, inhibited by maternal secretions before term, appears suddenly at birth.
Abstract: Concentrations of cortisol, corticosterone and cortisone in the plasma and adrenal glands, liver glycogen and plasma glucose of foetal, newborn and mother guinea-pigs were estimated during the last 6 days of pregnancy and throughout the first 24 h post partum. At the same time progesterone was measured in the plasma of the mother. During the prepartum rise in foetal plasma cortisol levels and liver glycogen, no significant change in the foetal adrenal cortisol content was observed. The plasma and adrenal cortisol concentrations of the mother were much higher than those observed in the foetus and increased significantly before parturition. In the mother as in the foetus, cortisone and corticosterone represent only a small percentage of corticosteroids compared with cortisol. These results indicate that the autonomous capacity of foetal adrenals, inhibited by maternal secretions before term, appears suddenly at birth.

Journal ArticleDOI
TL;DR: Differences were observed in the times of oviposition of eggs which ovulated in response to injections of either progesterone or a corticosteroid and it was suggested that the mechanism of action of progestersone and corticosterone operates through different endocrine pathways.
Abstract: 1. Pregnenolone, progesterone, deoxycorticosterone and cortico‐sterone were injected into hens between 16.30 and 17.00 h on the day of oviposition of the last egg of a sequence. 2. Pregnenolone did not affect ovulation, but all of the other steroids induced ovulation prematurely. 3. To induce premature ovulation in 50% of the hens, 82–31 μg± 0.06 μg, 23–86 μg±0.07 μg and 659–26 μg + 0.05 μg of progesterone, deoxycorticosterone and corticosterone, respectively were required for injection. 4. Differences were observed in the times of oviposition of eggs which ovulated in response to injections of either progesterone or a corticosteroid and it was suggested that the mechanism of action of progesterone and corticosteroids operates through different endocrine pathways.

Journal ArticleDOI
TL;DR: A possible causal relationship between the rhythm of growth and sex difference in the adrenal glands in rats is discussed.