Showing papers on "Corticosterone published in 1979"

Transport of Steroid Hormones Through the Rat Blood-Brain Barrier. Primary Role of Albumin-Bound Hormone

Abstract: These studies were undertaken to investigate (a) the permeability properties of the blood-brain barrier (BBB) to the major gonadal and adrenal steroid hormones, and (b) the role of the binding proteins of plasma (albumin and specific globulins) in the regulation of BBB steroid hormone transport. The permeability of the BBB to [(3)H]-labeled progesterone, testosterone, estradiol, corticosterone, aldosterone, and cortisol, was measured relative to [(14)C]butanol, a freely diffusable reference, in the barbiturate anesthetized rat using a tissue sampling-single injection technique. The isotopes were rapidly injected in a 200-mul bolus of Ringer's solution (0.1 g/dl albumin) via the common carotid artery and the percent extraction of unidirectional influx of hormone was determined after a single pass through brain: progesterone, 83+/-4%; testosterone, 85+/-1%; estradiol, 83+/-3%; corticosterone, 39+/-2%; aldosterone, 3.5+/-0.8%; and cortisol, 1.4+/-0.3%. The selective permeability of the BBB was inversely related to the number of hydrogen bonds each steroid formed in aqueous solution and directly related to the respective 1-octanol/Ringer's partition coefficient. When the bolus injection was 67% human serum, >95% of the labeled steroid was bound as determined by equilibrium dialysis. However, the influx of the steroids through the BBB was inhibited by human serum to a much less extent than would be expected if only the free (dialyzable) hormone was transported; progesterone, estradiol, testosterone, and corticosterone transport was inhibited 18, 47, 70, and 85% respectively, or in proportion to the steroid binding to plasma globulins. Rat serum (67%) only inhibited the transport of these four hormones, 0, 13, 12, and 69%, respectively, reflecting the absence of a sex hormone-binding globulin in rat plasma. However, neonatal rat serum (67%) inhibited progesterone, testosterone, and estradiol transport 0, 0, and 91%, respectively, consistent with the presence of an estradiol-binding protein in neonatal rat serum. The binding of steroid hormone to bovine albumin in vitro (as determined by equilibrium dialysis) was compared to albumin binding in vivo (as determined by the single injection technique). The ratio of apparent dissociation constant in vivo, K(D)(app), to the in vitro K(D) was: >>200 for progesterone, >200 for testosterone, 120 for estradiol, and 7.7 for corticosterone. Assuming the steady-state condition, the K(D)(app)/K(D) was found to be proportional to the BBB permeability for each steroid. These data demonstrate (a) the selective permeability properties of the BBB to the major steroid hormones is proportional to the tendency of the steroid to partition in a polar lipid phase and is inversely related to the number of hydrogen bond-forming functional groups on the steroid nucleus; (b) the presence of albumin in serum may bind considerable quantities of steroid hormone, but exerts little inhibitory effects on the transport of steroids into brain, whereas globulin-bound hormone does not appear to be transported into brain to a significant extent. Therefore, the hormone fraction in plasma that is available for transport into brain is not restricted to the free (dialyzable) fraction, but includes the larger albumin-bound moiety.

Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of Nτ-methylhistidine

Abstract: The role of glucocorticoids in regulating the rate of muscle protein breakdown was evaluated by measuring excretion of N(tau)-methylhistidine during administration of various doses of corticosterone to adrenalectomized rats. Groups of rats received daily subcutaneous injections of 0, 0.2, 0.5, 1.0, 5.0 or 10.0mg of corticosterone/day per 100g body wt. for 7 days, followed by 3 days without hormone treatment, after which they were killed. A group with intact adrenal glands served as an additional control. All animals were pair-fed with the untreated adrenalectomized group. No significant differences were noted in growth rate or N(tau)-methylhistidine excretion between the intact or adrenalectomized control groups, or those given 0.2, 0.5 and 1.0mg of corticosterone, whereas growth ceased and N(tau)-methylhistidine excretion rose markedly in the groups receiving 5 and 10mg of corticosterone. After these two high doses of corticosterone, but not after lower doses, there was a loss of weight of the gastrocnemius muscle per 100g of final body wt., but not of the soleus and extensor digitorum longus muscles. The two highest doses of corticosterone also resulted in an increase in liver weight per 100g of final body wt. Lower doses of corticosterone did not cause these changes. Plasma corticosterone concentrations, measured on the final day of injection and again at the time of killing, were decreased to near zero by adrenalectomy and were little raised by doses of 0.2 and 0.5mg daily, but were increased to within the normal range by the 1mg dose. At 5 and 10mg doses, plasma corticosterone concentrations were sustained at 2-3 times those of intact rats, and thus in the range reported for rats exposed to severe stress. Rats given 5 and 10mg doses of corticosterone had glycosuria, and showed considerably elevated concentrations of insulin in the plasma. It is concluded that plasma concentrations of glucocorticoids within the normal range do not regulate the rate of muscle protein breakdown, whereas excessive plasma concentrations of corticosteroids, equivalent to those observed in severe stress, can accelerate muscle protein breakdown.

Effects of lesions of the suprachiasmatic nuclei and of p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma, and on locomotor activity of rats.

Abstract: Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration. Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions. These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms.

Temporal changes in plasma adrenocorticotropin concentration after repeated neurotropic stress in male and female rats.

Abstract: To test the ability of the pituitary gland to secrete ACTH in response to repeated stress, 90-day-old male and female rats were subjected first to a 3-min psychological stress and then to a second identical stress 5, 10, or 15 min after the onset of the first stress. After decapitation 5, 10, 15, 20, 25, or 35 min after the onset of the second stress, plasma ACTH concentration was determined by bioassay, and plasma corticosterone was measured by a fluorometric method. Although the rate of increase in plasma corticosterone levels after the first stress was about 1.4 μg/100 ml-min in males and 2.1 μg/100 ml-min in females, 5-15 min after the onset of the first stress, no rapid inhibition of the second stress response appeared. Gradual hypersecretion of ACTH occurred in males after exposure to the second stress, and the resultant peak increment in plasma ACTH concentration was 2–3 times greater than the one observed in once-stressed rats. In females, a rapid and significant increase in plasma ACTH concentrat...

Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress

Abstract: Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.

Daily rhythms in adrenal responsiveness to adrenocorticotropin are determined primarily by the time of feeding in the rat.

Abstract: These experiments were done to determine: 1) whether feeding-related shifts in daily corticosterone rhythms are dependent upon changes in ACTH rhythms, 2) whether restricted feeding of rats results in abnormally high ACTH and corticosterone levels (i.e. stress), and 3) whether changes in either insulin or glucose levels might be the concomitants of feeding that change adrenal responsiveness to ACTH. Young male rats (80–90 g) on a 12-h light, 12-h dark cycle were allowed access to one of three diets for 2 h/day beginning either at lights off or lights on. The diets contained 3%, 4.5%, or 11% fat. A group of rats had ad libitum access to the food containing 4.5% fat. On day 20 of this regimen, rats were killed at 2- to 4-h intervals during the next 24 h, and plasma ACTH, corticosterone, insulin, and glucose were measured. Adrenal weight and corticosterone content were also determined. In none of these experiments was an ACTH rhythm demonstrable by analysis of variance. Neither ACTH levels nor adrenal and pl...

Loci of Action of Regulators of Aldosterone Biosynthesis in Isolated Glomerulosa Cells

Abstract: The effects of angiotensin II (All), ACTH, and potassium on early and late steps of aldosterone biosynthesis were studied in collagenase-dispersed cells from rat adrenal capsules and dog zona glomerulosa. Isolated cells were incubated with a cyanoketone derivative (WIN 19,578) to isolate the nearly and late portions of the biosynthetic pathway. In this way, the formation of pregnenolone and later steps of biosynthetic conversion in the absence of endogenous precursors could be measured independently during stimulation by the three regulators. During incubation for 3 h with 10 nM All, 10 nM ACTH, or 15 mM potassium, marked stimulation of pregnenolone production was observed in glomerulosa cells of both species. In rat glomerulosa cells, each of the three regulators also stimulated conversion of exogenous corticosterone to aldosterone. In dog glomerulosa cells, All and potassium, but not ACTH, stimulated the conversion of corticosterone to aldosterone. In rat glomerulosa cells, aldosterone production from e...

Effect of amphetamine on plasma corticosterone in the conscious rat.

Abstract: The effect of amphetamine (AMPH) on plasma corticosterone was studied in the conscious, unstressed rat. AMPH (0.5-5.0 mg/kg) produced a dose-dependent increase in plasma corticosterone. This rise in plasma corticosterone was not altered by the adrenergic blocking agents phenoxybenzamine or propranolol. In contrast, the serotonergic depleting agent p-chloroamphetamine significantly inhibited the AMPH-induced rise in corticosterone. In addition, the serotonergic blocking agent methysergide, but not cyproheptadine, inhibited the corticosterone increase induced by AMPH.

The role of corticosterone in the loss in immune function in the zinc-deficient A/J mouse.

Abstract: Previous studies from this laboratory have shown that zinc deficiency causes rapid atrophy of the thymus with subsequent loss of T-cell helper function in the young adult A/J mouse. The purpose of this investigation was to determine if zinc deficiency constituted a chronic stress on the mouse leading to the elevation of glucocorticoid levels which is known to destroy thymic lymphocytes. The results of these experiments indicate that zinc-deficient mice indeed have increased levels of plasma corticosterone (115 mug/100 ml plasma) compared to mice fed zinc-adequate diets (40 mug/100 ml plasma). A significant reduction in T-cell helper function, which occurred 4 days after this rise in steroid concentration, suggests that corticosterone may contribute to the loss in immunity; however, about half of the total loss in T-cell helper function occurred prior to the increase in plasma corticosterone and was due to other factors associated with the lowered zinc levels.

Aldosterone, deoxycorticosterone, corticosterone, and prolactin changes during the lifespan of chronically and spontaneously hypertensive rats.

Abstract: Male and female spontaneously hypertensive rats (SHR), which develop hypertension spontaneously with maturation, were autopsied at select time intervals from weaning to 28 months. Their blood pressure began to rise steeply at 4–5 weeks, reaching a zenith of 180–240 mm Hg after 4 months. Elevated blood pressures were maintained in both sexes. After 20 months, the male SHR began to die of myocardial infarction and hypotensive crisis. Heart and adrenal gland weight increased progressively not only during the phase of rapidly rising blood pressure but also during the period of plateaued but sustained high blood pressure. RIA of plasma levels of aldosterone, deoxycorticosterone, corticosterone, and PRL, under both quiescent and mildly stressful conditions, demonstrated that the pituitaryadrenal axis of SHR progressively increases its propensity to respond to stress with maturation. This capacity to respond to stress was maintained despite the severe high blood pressure and the attainment of relative old age, i...

Modulation of behavioral inhibition in appetitive extinction following manipulation of adrenal steroids in rats: implications for involvement of the hippocampus.

Abstract: Corticosterone, the principal glucocorticoid in the rat, binds selectively to the CA1 pyramidal neurons of the hippocampus where the hormone has been demonstrated to exert a moderate chronic suppression of spontaneous activity In the first experiment of the current study, the functional behavioral significance of this hormone--brain interaction was investigated in the extinction of an appetitive runway response in normal rats and those with lesions of the hippocampus During extinction, half of the animals in each group were given daily subcutaneous injections of corticosterone Whie the classical retardation effect of hippocampal lesions on appetitive extinction was replicated, hormone treatment was without effect in normal or hippocampally damaged subjects The absence of a hormone effect in normals was primarily attributed to a saturated limited-binding system operating in the normal animal Experiment 2 tested this notion, repeating the first experiment, with adrenal-ectomized (ADX), ADX + corticosterone replacement, and normal groups of animals Adrenalectomy produced a striking facilitation of extinction which was speculated to be the result of a hyperactive inhibitory neural organ free from an inhibitory endocrine feedback Corticosterone treatment normalized the progress of extinction in ADX animals, providing support for the afore-mentioned speculation In the normal animal, it appears that a stress-induced surge in hormone level interacts with a limited-capacity neural binding to produce a transient dynamic range of behavioral disinhibition, perhaps promoting persistence during initial stages of frustrative nonreward in moderate stress tasks

Direct effect of corticosterone upon insulin secretion studied by three different techniques.

Abstract: The immediate effect of corticosterone upon insulin secretion rates estimated by three different techniques (perfusior of isolated rat pancreas and perifusion or incubation of isolated islets of Langerhans) was studied for one hour. Three corticosterone concentrations were used: 0.02, 0.2 or 20 mg/l. With 4.2 mmol/l glucose, corticosterone did not affect insulin secretion, whereas, with a stimulating glucose concentration (16.7 mmol/l), insulin secretion was inhibited by the three corticosterone concentrations tested during incubation experiments, and by only the two physiological ones (0.02 and 0.2 mg/l) during islets perifusion and pancreas perfusion experiments. Moreover the inhibitory effect appeared more rapid with perifused islets than perfused pancreas, where only the second insulin secretory phase was disturbed.

Comparison of the effects of 2-deoxyglucose and immobilization on plasma levels of catecholamines and corticosterone in awake rats.

Abstract: In rats, both forced immobilization and 2-deoxyglucose (2DG) administration evoke increases in sympatho-adrenal medullary release of catecholamines and adrenal cortical secretion of corticosterone. To examine the specificity and mediation by the central nervous system of these responses, plasma levels of epinephrine (from the adrenal medulla), norepinephrine (from sympathetic nerves), and corticosterone were determined during immobilization and after ip or intracerebroventricular administration of 2DG. After 2DG, plasma levels of epinephrine reached a peak within 15 min, while those of corticosterone were maximal at about 1 h. There was a clear relationship between dose of 2DG and the increases in epinephrine and corticosterone, but plasma levels of norepinephrine were increased only at the highest dose (1000 mg/kg) of 2DG. Severing the splanchnic nerve prevented the elevation in levels of epinephrine but did not alter the increase in corticosterone. The dose of 2DG (500 mg/kg) which elicited the same cor...

Endocrine interaction of the thymus with the hypohysis, adrenals and testes: effects of two thymic extracts.

Abstract: The concentration of ACTH, corticosterone, LH and testosterone in the plasma of rats have been measured in normal, thymectomized and sham-operated rats. A group of rats, thymectomized at birth, received two i.p. injections weekly of two thymic extracts, each prepared in a separate way. Neonatal thymectomy was followed by the appearance of a transitory wasting disease during which a hormonal unbalance was manifest. Plasma corticosterone and ACTH levels increased at first at 30 days after thymectomy and then decreased at 60 days. The levels of the different hormones returned to normal by 90 days. The injections of thymic extracts rectified all these perturbations. The plasma levels of testosterone and corticosterone of hypophysectomized rats were compared to those of hypophysectomized and thymectomized animals. Results suggested that the thymus has a direct action of the adrenal cortex and in indirect action on the testes. The indirect effect is probably mediated through the hypophysis.

Acute Self-Suppression of Corticosteroidogenesis in Isolated Adrenocortical Cells

Abstract: The relation between steroidogenesis induced by ACTH and that induced by exogenous concentrations of glucocorticoids was studied in isolated adrenocortical cells. Exogenous corticosterone and cortisol, in concentrations within the production capacity of the adrenal gland, suppressed steroidogenesis induced by ACTH in rat and beef cells, respectively. The precursors pregnenolone and progesterone enhanced steroidogenesis in both rat and beef cells. Aldosterone in rat cells and 17 beta-estradiol in rat and beef cells had little if any effect on steroidogenesis. Either suppression or stimulation by exogenous steroids was acute, that is, after 2-h incubation for rat cells and 1-h incubation for beef cells. A direct suppressive action of end product glucocorticoids is indicated. This observed self-suppression of adrenocortical cells suggests the existence of a mechanism for the find adjustment of steroidogenesis that operates in addition to the classical control exerted by the anterior pituitary.

Effect of stress, adrenocorticotropin or corticosteroid treatment, adrenalectomy, or hypophysectomy on hypothalamic immunoreactive adrenocorticotropin concentrations.

Abstract: Despite variations in plasma and/or pituitary ACTH concentrations, no changes in median eminence or medial basal hypothalamic immunoreactive ACTH-like concentrations were seen in rats studied 6 weeks posthypophysectomy,12 h or 28 days after bilateral adrenalectomy, 6 days after implantation of corticosterone pellets (75 mg), after dexamethasone administration (300 μg/100 g BW, ip, twice daily for 4 days), or after chronic immobilization stress. The lack of concordant variation of brain, pituitary, and plasma ACTH concentrations further supports the suggestion of a nonpituitary, central nervous system origin of some portion of brain immunoreactive ACTH-like activity.

The action of nicotine on the pituitary-adrenal cortical axis.

Abstract: Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow.

Glucocorticoid Regulation of Prolactin Receptors on Mammary Cells in Culture

Abstract: Mouse mammary epithelial cultures were examined for the ability to specifically bind [125I]PRL after cultivation on floating collagen gels. Corticosterone, particularly hydrocortisone, were effective in increasing the ability of mouse mammary cells to bind [125I]PRL. The absence of a glucocorticoid in the medium resulted in a loss of PRL binding during the 3 days in culture. 17β-Estradiol, progesterone, and aldosterone at equal molar concentration had no or only a small effect in increasing [125I]PRL binding.

Progesterone suppression of estrogen-stimulated prolactin secretion and estrogen receptor levels in rat pituitary cells.

Abstract: The effects of progesterone, testosterone, corticosterone,and TRH on estrogen-induced PRL synthesis andcytoplasmic estrogen receptor levels were studied in a clonalstrain of rat pituitary tumor cells (GH3). PRL synthesis wasmeasured as the amount of hormone which accumulated in theculture medium (micrograms per mg cell protein/24 h), andreceptor levels were measured as specific [3H]estradiol bindingin the GH3 cells (picomoles per mg cell protein). 17Β-Estradiol (10-8M) stimulated PRL synthesis 2.1-fold, while progesterone (10-6 M) and corticosterone (10-6 M) bothdecreased PRL synthesis to about 0.9 times control levels. Testosterone(10-6 M) and TRH (3 x 10-7 M) increased PRL synthesis1.2- and 1.8-fold, respectively. The combined treatmentwith 17Β-estradiol plus progesterone increased PRL synthesis1.2-fold, while the simultaneous treatment with either 17Β8-estradiol and corticosterone or 17Β-estradiol and testosterone stimulated PRL synthesis to values not significantly different from those in cultures tre...