Showing papers on "Corticosterone published in 1978"

Plasma concentrations of total and free corticosterone during development in the rat.

Abstract: A sensitive protein-binding assay has been used to measure plasma concentrations of total corticosterone during postnatal development in the rat. These concentrations were extremely low on days 6--12, showed a significant rise by day 14, and then continued to rise until peaking on day 24. Plasma titers of corticosteroid-binding globulin rose even more dramatically from day 12 onward. Consequently, the percentage of total plasma corticosterone, which was protein-bound, showed a gradual rise from 78% on day 12 to 98% on day 24. Despite this trend, when concentrations of free corticosterone were calculated, they were found to have a developmental profile very similar to that of total corticosterone. Assay of jejunal lactase and sucrase in the same animals that were used for the corticosterone studies showed that the ontogenic rise of both total and free corticosterone preceded the developmental changes in the activities of these enzymes by approximately 2 days. The data suggest that the rise in free corticosterone that begins on day 14 acts as a cue for enzymic changes in both liver and intestine.

Memory facilitating and anti-amnesic effects of corticosteroids

Abstract: The effects of corticosterone, hydrocortisone and dexamethasone on retention of active and passive avoidance training were studied in male mice. Posttraining administration of any of the hormones facilitated subsequent retention test performance of poorly trained mice when tested one week after training and drug administration. The optimum dose of dexamethasone was 4 mg/kg, while corticosterone and hydrocortisone were effective at 30 and 40 mg/kg, respectively. Dexamethasone significantly facilitated retention when administered up to 150 min but not at 210 min after training. It was further determined that dexamethasone blocked the amnesic effect of two but not four successive injections of anisomycin in both active and passive avoidance tasks. Corticosterone and dexamethasone when administered to anisomycin-injected mice caused only a small, transient increase in the protein synthesis inhibition. In saline-injected control mice, the hormones also caused a small inhibition of protein synthesis which disappeared quickly. Plasma corticosterone levels were measured in mice trained and given anisomycin, cycloheximide or saline. Plasma corticosterone levels were reduced 43% by anisomycin and 89% by cycloheximide. In both cases the corticosterone levels subsequently increased rapidly after the inhibitor injection and were elevated by about 5 times above control levels at 130 min after the inhibitor injection. The results are discussed in terms of the effect of central stimulant action of corticosteroids on memory formation.

Nycthemeral rhythm in adrenal responsiveness to ACTH.

Abstract: Adrenal adenosine 3',5'-cyclic monophosphate (cAMP) and corticosterone responses to exogenous ACTH were found to be about 2.5 times greater in the evening (at lights off) than in the morning (at lights on) in rats. The rhythm in adrenal responsiveness to ACTH was found to persist in rats treated with dexamethasone 15 and 3 h before exogenous ACTH (in the presumed absence of a rhythm in endogenous ACTH). Treatment with p-chlorophenylalanine did not affect the daily rise in circulating ACTH levels but did abolish the rhythm in adrenal responsiveness to ACTH. The magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude of the rhythm in ACTH. Because the rhythms are dissociable, we conclude that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels.

Selective Depression of Serum Growth Hormone During Maternal Deprivation in Rat Pups

Abstract: Maternal deprivation was associated with a decline in immunoreactive growth hormone in the serum of rat pups. Pups that were returned to the mother showed a rapid reversal in this deprivation-induced decrease. The change in growth hormone concentration was not accompanied by changes in the concentrations of prolactin, thyrotropin, or corticosterone in the serum, but were correlated with alteration in the activity of ornithine decarboxylase in the brain. Treatment of neonatal rat pups with cyprohepatadine, a serotonin antagonist that suppresses growth hormone secretion, resulted in a significant decline in both serum growth hormone concentration and brain ornithine decarboxylase activity. These findings suggest that maternal deprivation elicits a specific suppression of growth hormone release which mediates the decrease in ornithine decarboxylase activity. The study is consistent with clinical findings of impaired growth hormone "responsitivity" in human maternal deprivation syndrome.

Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells.

Abstract: Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase- dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 ± 0.4 (SE) × 109 M-1) and intact glomerulosa cells (1.8 ± 0.3 × 109 M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium- dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 × 10-11, equivalent to normal blood levels of A II in rats (5 × 10-11). The maximum increa...

Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery.

Abstract: In order to obtain the still lacking reference data of individual plasma steroids in the immediate postnatal period needed for the assessment of adrenocortical function in various neonatal maladaptation syndromes, aldosterone (A), corticosterone, deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone were simultaneously followed in the same human newborn in a single 250–500 µl peripheral plasma sample obtained at constant times during the first week of life using a mechanized Sephadex LH-20 multicolumn chromatography and standardized RIAs. Mean concentrations in 12 spontaneously delivered full term newborns of either sex and in paired umbilical (UV) and peripheral maternal (MV) venous plasma are given in the table. Besides significant maternoumbilical gradients in each steroid, DOC, P, 17-OHP, and cortisone, originating predominantly from the fetoplacental unit, disappear rapidly with steadily increasing half-lives. A, corticosterone, and cortisol, however, r...

Some Effects of Adrenalectomy in the Fatty Rat

Abstract: Function of the pituitary-adrenal axis was examined in lean and genetically obese fatty (Zucker) rats. The diurnal rhythms of plasma corticosterone and plasma ACTH were similar in both groups. The secretion of corticosterone by adrenal glands incubated in vitro with graded doses of ACTH was also comparable in lean and fatty rats. Adrenalectomy reduced food intake and weight gain in the fatty rats to levels similar to those in the lean animals and raised plasma ACTH to the same level. The injection of corticosterone (2 and 10 mg/day) increased food intake more in adrenalectomized fatty rats than in the corresponding lean ones. Progesterone increased food intake similarly in both groups. The enhanced responsiveness to corticosterone could account for many of the metabolical defects in the fatty rat.

Properties of rat adrenal zona reticularis cells: preparation by gravitational sedimentation

Abstract: An enriched fraction of zona reticularis cells was obtained by unit gravity sedimentation of decapsulated adrenal glands from female rats. From light microscopic and ultrastructural studies of the whole gland and the isolated cell fractions, the zona reticularis cells of the adrenal gland can be classified mainly on the bases of size, position and mitochondrial morphology. This cell population consists of two types of cell, the 'true' zoma reticularis cells (Type I, modal diameter 9 micrometer), which usually constitute 90% of the isolated reticularis fraction and 80% of the intact reticularis tissue, and cells (Type II, modal diameter 13 micrometer) with fasciculata-like properties (rich in lipid and spherical mitochondria with vesicular cristae). Staining of the cell preparation for 3beta-hydroxysteroid dehydrogenase activity also demonstrates the existence of two types of cell in the zona reticularis. The zona reticularis cell fraction, like the zona fasciculata cell fraction, was capable of producing the subsequent steroids from radioactive pregnenolone: corticosterone, deoxycorticosterone, 18-hydroxydeoxycorticosterone, 11-dehydrocorticosterone, progesterone and androstenedione. However, the pattern of steroid production differed markedly between the zona reticularis and zona fasciculata cells, particularly with respect to the production of deoxycorticosterone and corticosterone (and its correlated steroids, 11-dehydrocorticosterone and 18-hydroxydeoxycorticosterone). When R (the ratio of deoxycorticosterone : corticosterone plus 11-dehydrocorticosterone) for the purest preparation of reticularis cells was compared with R for the corresponding preparation of fasciculata cells, the normalized ratio was found to be 6.4, 16.4 and 20.1 in three experiments. The pattern of production of androstenedione per cell was similar in the reticularis and fasciculata cell fractions. The exact mechanism for the altered pattern of steroid metabolism remains to be elucidated. However, these results establish that the corticosteroids produced by the cells of the zona reticularis may be quantitatively, if not qualitatively, different from those produced by the zona fasciculata cells.

Diurnal changes in serum metabolites and hormones in lean and obese Zucker rats.

Abstract: A study of diurnal patterns of serum hormone levels was made in genetically lean and obese Zucker rats. Serum glucose and insulin were elevated in the obese through the 24-hour period; immunoreactive insulin being 12 times higher in the obese rat. A similar pattern of serum hormone levels in lean and obese rats was found for triiodothyronine, thyroid stimulating hormone and prolactin. At peak levels, prolactin was 2.5 times higher in lean than obese rats (P is less than .01). Thyroxine levels tended to be lower in the obese rats throughout the sampling periods when compared to lean rats. Growth hormone levels were severely depressed in the obese rat with the largest differences between lean and obese rats being observed during the light periods of the cycle. These differences in growth hormone secretion may be responsible for the impaired nitrogen retention in the obese rat. Serum levels of corticosterone were highest at the beginning of the dark cycle and decreased drastically thereafter in the lean rats. The obese rat did not exhibit a distinct pattern of corticosterone secretion and tended to be elevated throughout the periods tested.

Specific interaction of corticosteroids with binding sites in the plasma membranes of the rat anterior pituitary gland

Abstract: The binding of glucocorticoids to a crude fraction of rat pituitary plasma membranes and to solubilized membrane proteins was measured. The binding characteristics were similar to those exhibited by transcortin: radioactive corticosterone was bound to a greater extent than radioactive dexamethasone and labelled corticosterone, but not labelled dexamethasone, was displaced by unlabelled corticosterone, deoxycorticosterone and progesterone. A Scatchard plot of the binding data revealed the presence of a binding material with a dissociation constant of about 3.2 nmol/l, which sedimented at 4S after sucrose density-gradient centrifugation. It was found that the number of binding sites was inversely related to the concentration of corticosterone in the circulation and was increased after long-term adrenalectomy. These data suggest that a material similar to transcortin is complexed to the plasma membrane of rat pituitary cells.

Cyproteroneacetate and ACTH adrenal function.

Abstract: Cyproteroneacetate, an antiandrogenic and gonadotropin-inhibiting steroid, has a marked ACTH suppressive effect. In rats, adrenal atrophy and severe impairment of ACTH and corticosterone responses to stress are induced by a 10-day treatment with 3–0.75 mg/100 g BW cyproteroneacetate/day. Two weeks after cessation of treatment, the ACTH adrenal system has not yet recovered. The ACTH suppression is evident 6 h after a single dose. In 25 human volunteers, a single dose of 200 mg cyproteroneacetate impaired their ACTH and 11-deoxycorticosteroid response to 1 g metyrapone. A similar impairment was seen in 12 women on sequential treatment with cyproteroneacetate and ethinyl estradiol. In 4 out of 11 children treated for precocious puberty, random plasma ACTH and cortisol measurements, cortisol responses to ACTH, and ACTH and cortisol responses to insulin-induced hypoglycemia revealed severely impaired ACTH adrenal function. Questionable impairment was found in 2 out of 11 and normal function in 5 out of 11 chil...

Some age-related changes in pituitary-adrenal function in the male laboratory rat.

Abstract: Changes in the pituitary-adrenal axis have been investigated as a function of age (2 1/2 to 26 mo) in the male laboratory rat (CFY-Sprague Dawley). Ether stress was used to challenge the pituitary-adrenal axis and blood samples (peripheral and adrenal venous effluent) taken for measurement of corticosterone using the competitive protein-binding assay and ACTH by the increase in corticosteroidogenesis in isolated rat adrenal cells. The results show that there was an increase of basal ACTH levels with increase in age which might be correlated with the degenerative changes in the adrenal cortex at old age. No age difference was observed in the 2 1/2-min stress levels. However, 15-min stress resulted in a further increment of ACTH levels, which was not found in old animals. No age-related differences in the basal and stress levels of corticosterone was observed, and, hence, adrenocortical function would seem not to be impaired in old age.

Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.

Abstract: The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin II formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.

Plasma mineralocorticoids, plasma renin, and urinary kallikrein in salt-sensitive and salt-resistant rats.

Abstract: Plasma aldosterone, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (180H-DOC), and corticosterone were measured in Dahl salt-sensitive (S) and salt-resistant (R) rats. Plasma corticosterone and DOC were not different between strains but plasma aldosterone was decreased and plasma 180H-DOC increased in S compared to R. Plasma renin activity and urinary kallikrein excretion were both lower in S than R. Urinary kallikrein is known to vary directly with mineralocorticoid activity and 180H-DOC is a weak mineralocorticoid. The lower urinary kallikrein in the presence of elevated 180H-DOC could mean that urinary kallikrein differences between S and R are under independent genetic control from 180H-DOC.

Effects of steroid hormones on the level of corticotropin messenger RNA activity in cultured mouse-pituitary-tumor cells.

Abstract: Studies have been made with the mouse pituitary tumor cell line AtT-20 in culture to determine whether or not the suppression of pituitary corticotropin messenger RNA activity observed upon the administration of glucocorticoids to adrenalectomized rats is due to a direct action of these steroid hormones on the pituitary. The levels of corticotropin messenger RNA activity in AtT-20 cells treated with various steroid hormones were measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The addition of dexamethasone to culture medium reduced the level of corticotropin messenger RNA activity to 30-40% of that in untreated cells. Corticosterone and cortisol exhibited a suppressive effect to a lesser extent. In contrast, nonglucocorticoids such as testosterone and 17beta-estradiol were essentially ineffective. These results indicate that at least part of the glucocorticoid action is exerted directly on the pituitary to suppress corticotropin messenger RNA activity.

Perinatal changes in plasma and adrenal corticosterone and aldosterone concentrations in the mouse.

Abstract: The concentrations of corticosterone and aldosterone in the plasma and adrenal glands of foetal, newborn and mother mice were estimated during the last 4 days of pregnancy and throughout the perinatal period. The level of corticosterone in the maternal and foetal plasma fell from day 17 of gestation until birth, and then remained stable. Whereas the corticosterone content of the maternal adrenal glands did not change significantly, that of the foetal adrenal glands reached a peak on day 19 of gestation. At every stage of gestation, the level of corticosterone in the maternal plasma was higher than that in the foetus. Changes in the concentration of aldosterone in the foetal plasma and adrenal glands were similar and characterized by peak values at birth. In the mother during the last 4 days of pregnancy, the level of aldosterone in the plasma was higher than in non-pregnant mice, but lower than that in the foetus.

Effects of antiserum to adrenocorticotropin on adrenal growth and function.

Abstract: The trophic action of ACTH was investigated in intact rats by selective neutralization of endogenous hormone with specific antibodies. Administration of antiserum to ACTH to male Sprague-Dawley rats ranging in age from 3–12 weeks for a period of 6–10 days had no effect on adrenal weight but caused a highly significant decrease in serum corticosterone levels. The ability of adrenocortical cells isolated from antiserum-treated animals to produce corticosterone in response to exogenous ACTH was also significantly lower than that of adrenocortical cells derived from normal rabbit serum-treated animals. Administration of ACTH antiserum to unilaterally adrenalectomized animals did not prevent the increase in weight, cell number, and DNA content of the remaining adrenal gland. However, the steroidogenic capacity of adrenocortical cells from antiserum-treated animals was significantly lower in comparison with the capacity of cells obtained from the adrenals of unilaterally adrenalectomized rats treated with norma...

Evidence for the role of adrenocortical hormones in the regulation of noradrenaline and dopamine metabolism in certain brain areas.

Abstract: 1 Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time-dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum. 2 Catechol-O-methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation. 3 Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham-operated controls. 4 Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation.