Showing papers on "Corticosterone published in 1981"

Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro.

Abstract: The direct effects of glucocorticoids on testicular LH receptor content and steroidogenesis were studied in vivo and in vitro. Immature hypophysectomized rats were treated with varying doses of dexamethasone, corticosterone, or a synthetic progestin, 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020). Some animals were also treated concomitantly with FSH to prevent the hypophysectomy-induced decrease in testis functions. At the end of 5 days of treatment, testicular LH/hCG receptor content was measured by [125I]hCG binding assay while steroidogenic responsiveness was measured by in vitro incubation of testes. Dexamethasone decreased testicular LH receptor in control and FSH-treated hypophysectomized rats in doses as low as 10 microgram/day, whereas corticosterone (10 microgram/day) decreased testicular LH receptor in the FSH-treated rats but had no effect in rats not treated with FSH. In contrast, R5020 had no effect on testicular LH receptor content. In vivo treatment of hypophysectomized rats with FSH increased both basal and hCG-stimulated production of androstanediol in vitro. In contrast, concomitant treatment with dexamethasone, but not R5020, decreased both basal and hCG-stimulated testicular androstanediol production. The direct effect of glucocorticoids on testicular steroidogenic potentials was also studied in primary culture of testicular cells obtained from adult hypophysectomized rats. Treatment of cultured testicular cells wtih hCG increased testosterone production. The addition of various natural and synthetic glucocorticoids, but not R5020, to hCG-treated cells decreased testosterone production in a dose- and time-related manner (triamcinolone greater than or equal to dexamethasone greater than cortisol greater than or equal to corticosterone). A 40% decrease in testosterone production was apparent at 6 h after addition of 10(-7) M dexamethasone to hCG-treated cells. These results demonstrate the direct inhibitory effect of glucocorticoids on testicular LH receptor content and steroidogenesis, suggesting the adrenal glucocorticoids may regulate testis functions.

Adrenal sensitivity to adrenocorticotropin varies diurnally.

Abstract: To further characterize diurnal changes in the rhythm in adrenal responsiveness to ACTH, we have measured ACTH distribution volume, MCR, and t 1/2. These do not change between morning and evening in groups of untreated, dexamethasone-pretreated, or hypophysectomized female rats. To characterize the nature of the change in adrenal responsiveness to ACTH, dexamethasone-pretreated rats were infused for 2 h with a variety of doses of ACTH in the morning and evening. The adrenal response to an infusion rate of ACTH that maximally stimulated the adrenals (200 pg/100 g BW.min) was the same in the morning and evening, showing that adrenal capacity does not change. However, infusion of ACTH at lower rates (50-100 pg/100 g BW.min) revealed that the slope of the steroid response curve increased between morning and evening, demonstrating a diurnal change in adrenal sensitivity to ACTH. These results together with previous data showing that the magnitude and time course of the adrenal cAMP response to ACTH changes diurnally strongly suggest that ACTH receptor affinity or coupling with adenylate cyclase changes diurnally. In other experiments, plasma ACTH and corticosterone levels were determined in groups of young and adult male and adult female untreated rats killed at 4-h intervals around the clock. Peak sensitivity to ACTH was found at lights-out, and trough sensitivity was found at lights-on, suggesting that the experimentally demonstrated rhythm occurs normally.

Effects of paraventricular lesions on stimulated ACTH release and CRF in stalk-median eminence of the rat.

Abstract: The effects of destroying the paraventricular nucleus (PVN) of the rat hypothalamus on pituitary-adrenal function were studied. Four days after PVN lesions were placed with a rotating knife, the basal plasma corticosterone level was normal, but the corticosterone response to electrical stimulation of the medial basal hypothalamus, surgical trauma, and ether-venesection stress was significantly inhibited. Four and 8 days after PVN lesioning and adrenalectomy, the basal plasma ACTH level was lower, and the rise of plasma ACTH level elicited by a 3-min ether inhalation was significantly smaller than in the adrenalectomized controls. Corticotropin-releasing factor (CRF) activity in the stalk-median eminence extracts from PVN-lesioned rats was significantly less than in the control extracts. The weight of the adrenals was decreased by both 2 and 4 wk after PVN destruction, and 2 wk after hemiadrenalectomy, the compensatory adrenal hypertrophy was inhibited. The plasma corticosterone response to ether-venesection stress was inhibited only temporarily because it returned to normal by the end of the 4th postoperative week. The results are consistent with the hypothesis that a substantial portion of CRF-containing fibers in the stalk-median eminence region either originate from or run though the PVN or its immediate vicinity.

Return of pituitary-adrenal function after adrenal enucleation or transplantation : diurnal rhythms and responses to ether

Abstract: Adrenocortical diurnal rhythms and responses to ether vapor were studied in rats 1, 3, and 5 weeks after bilateral adrenal enucleation, autotransplantation, or sham transplantation in order to 1) determine whether diurnal rhythms in the plasma corticosterone concentration and adrenal responsiveness to ACTH are dependent on innervation of the adrenals, 2) compare regeneration of function of transplanted and enucleated adrenals, and 3) investigate adrenal mass-related nonsteroidal inhibition of ether-stimulated ACTH secretion. Rats in both enucleate and transplant groups exhibited significant morning-evening differences in adrenal and plasma corticosterone concentrations and significant adrenocortical responses to ether 3 and 5 weeks, but not 1 week, after surgery. The morning-evening differences in corticosterone concentration occurred in the absence of significant morning-evening variation in the plasma ACTH concentration, supporting our previous finding of a diurnal rhythm in adrenal responsiveness to ACTH. The responsiveness rhythm cannot be dependent on adrenal nerves unless transplanted adrenals receive functionally specific reinnervation within 3 weeks. The processes of regeneration of function after enucleation and after transplantation are similar; there were no differences in plasma or adrenal corticosterone values between rats in enucleate and transplant groups at any time or under any condition tested. As regeneration progressed, plasma ACTH responses to ether declined in both enucleate and transplant groups in the absence of changes in plasma corticosterone feedback. These results support our previous finding of adrenal mass-related nonsteroidal suppression of ACTH responses to ether.

Plasma Aldosterone and Corticosterone Responses to Adrenocorticotropin, Angiotensin, Potassium, and Stress in Spontaneously Hypertensive Rats

Abstract: The responses of plasma aldosterone and corticosterone to ACTH, angiotensin II (AII), and potassium chloride (KCl) infusion and the aldosterone, corticosterone and PRA responses to immobilization stress were studied in 2-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive controls. Basal levels of plasma aldosterone and corticosterone were greater and PRA was less in the SHR than in the WKY. Aldosterone and corticosterone responses to graded AII were similar in both groups. Aldosterone and corticosterone responses to graded doses of KCl and ACTH, however, were significantly greater in SHR than in WKY normotensive rats. Plasma corticosterone, PRA, and aldosterone responses to immobilization stress were reduced in SHR compared to WKY. At 2 months of age, blood pressure was definitely elevated in SHR and was associated with low PRA and relatively high basal levels of aldosterone and corticosterone. Discordance between the renin-angiotensin system and mineralocortic...

The Metabolism and Mechanism of Action of Aldosterone

Abstract: ALTHOUGH the clinical importance of the adrenal cortex in the regulation of electrolyte balance had long been realized (1), it was not until the early 1950s that the major regulatory steroid, aldosterone, was isolated and identified by Simpson et al. (2). Simpson and Tait used a sensitive mineralocorticoid bioassay based on changes of urinary 24Na/42K ratios in adrenalectomized rats to help isolate aldosterone (3). Aldosterone is still the most potent mineralocorticoid known: 30–50 times more potent than deoxycorticosterone and at least a thousand times more active than the glucocorticoids, cortisol and corticosterone. Aldosterone's greater potency is balanced by a reduced secretory rate compared with most other adrenal steroids (4, 5). Its synthesis, exclusively by the zona glomerulosa of the adrenal cortex, is responsive to dietary sodium and potassium manipulations and more acutely to ACTH, plasma potassium concentrations, and the renin-angiotensin system (5, 6). Many of the initial investigations were...

Hypersensitivity of spontaneously hypertensive rats (SHR) to heat, ether, and immobilization.

Abstract: The responses to immobilization, ether, and heat of spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (S-D) were compared. Hyperglycemia reached a maximum within 5 min of exposure and was most intense in SHR. There were no differences in the pituitary content of GH or PRL between the SHR and S-D. Circulating GH levels were especially depleted in SHR 15 min post exposure, with rebound to high blood levels at 1 h. Circulating PRL levels were slightly higher in quiescent SHR vs. S-D but surged to much higher levels post exposure in SHR vs. S-D. Postexposure blood corticosterone and aldosterone levels rose to much higher levels in SHR vs. S-D. Although the blood glucose, GH, PRL, corticosterone, and aldosterone levels are similar in hypertensive SHR and normotensive S-D under quiescent conditions, SHR appear to be much more sensitive and respond more vigorously to heat, ether, and immobilization. It is suggested that abnormal activity of the hypothalamic-pituitary system may play a ro...

Corticosterone increases the amount of protein 1, a neuron-specific phosphoprotein, in rat hippocampus.

Abstract: Corticosterone increased the amount of the neuron-specific phosphoprotein protein 1 in the hippocampus, a brain region rich in corticosterone receptors, but not in several brain regions that contain relatively few corticosterone receptors.

Mechanisms of Inhibition of Aldosterone Secretion by Adrenocorticotropin

Abstract: The mechanisms by which prolonged administration of ACTH causes a decrease in aldosterone secretion were studied in the rat. After 6 days of treatment with ACTH (2 U/day), blood corticosterone was elevated and plasma aldosterone was decreased in rats maintained on either a normal or low sodium diet. PRA was also decreased, probably secondary to increased sodium and/or fluid retention. In collagenase-dispersed glomerulosa cells from adrenals of ACTH-treated rats, angiotensin II receptors were markedly decreased, as were the in vitro aldosterone responses to angiotensin II, ACTH, 8- bromo-cAMP, and potassium. However, the production of deoxycorticosterone and precursor steroids was increased, indicating the presence of a block in the late aldosterone biosynthetic pathway. Measurement of the activity of biosynthetic enzymes of the steroidogenic pathway in isolated mitochondria revealed an 80% increase in side-chain cleavage enzyme in both glomerulosa and fasciculata mitochondria from ACTH treated rats. Altho...

Elevation of Serum Corticosterone Concentrations in Rats by Pergolide and Other Dopamine Agonists

Abstract: Pergolide, a dopamine agonist, elevated serum corticosterone concentrations in rats. The elevation was dose dependent, a maximum effect being produced at a dose of 0.3 mg/kg, ip. The serum corticosterone concentration was highest 30–60 min after pergolide injection and had returned to normal by 4 h. Spiperone and haloperidol, known dopamine antagonists, blocked the increase in serum corticosterone. Metergoline and mianserin did not alter the increase in serum corticosterone caused by pergolide, but these serotonin antagonists prevented the increase caused by quipazine, a serotonin agonist. Haloperidol did not influence serum corticosterone elevation by quipazine, but spiperone partially antagonized quipazine's effect atdoses higher than those required to prevent the effect of pergolide (spiperone is known to block some serotonin receptors as well as dopamine receptors). The ED 50 for spiperone in antagonizing serum corticosterone elevation by pergolide was 0.003– 0.01 mg/kg whereas the EDr,o for spiperone...

The 21-Hydroxylase Activity in the Glomerulosa and Fasciculata of the Adrenal Cortex in Congenital Adrenal Hyperplasia*

Abstract: In the two clinical syndromes of congenital adrenal hyperplasia due to a 21-hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18-hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17-deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect.

Rapid glucocorticoid inhibition of vasoactive intestinal peptide-induced cyclic AMP accumulation and prolactin release in rat pituitary cells in culture

Abstract: Vasoactive intestinal peptide (VIP) stimulates both adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and prolactin release in normal rat pituitary cells in culture. cAMP accumulation is significant (P less than 0.01) at VIP concentrations as low as 1 nM and reaches a maximum with 0.1 microM. Addition of dexamethasone as early as 15 min before VIP inhibits VIP stimulation of both cAMP production and PRL secretion. The rapid inhibition is dose-dependent: it appears at doses as low as 0.01 pM and is complete at 1 pM dexamethasone. Increasing concentrations of dexamethasone induce a noncompetitive type of inhibition, as shown by the decrease in Vmax with no change in the apparent Km for VIP. Cycloheximide (1 mM) counteracts the inhibitory effect of dexamethasone on VIP-induced cAMP production, which suggests the involvement of a rapid protein synthesis mechanism. Ru-26988, a specific glucocorticoid devoid of any mineralocorticoid activity and which does not bind to intracellular transcortin-like component, also produces an inhibition of VIP-induced cAMP accumulation. Corticosterone also inhibits VIP-induced cAMP production but at concentrations higher than those of dexamethasone. In contrast, aldosterone, progesterone, estradiol, and testosterone have no effect. These results demonstrate that, in normal rat pituitary cells in culture, glucocorticoids at physiological concentrations rapidly inhibit the cAMP production and prolactin release induced by VIP by acting through specific glucocorticoid receptors.

Ontogenesis of Glucocorticoid Receptors in Anterior Pituitary Gland: Transient Dissociation among Cytoplasmic Receptor Density, Nuclear Uptake, and Regulation of Corticotropic Activity*

Abstract: The present investigation was undertaken to define the developmental pattern of glucocorticoid binding to the anterior pituitary gland and ascertain whether that binding correlated to modulation of corticotropin-releasing factor-induced release of ACTH. Scatchard analysis of data revealed the presence in cytosol (besides classical receptor sites interacting with both [3H]dexamethasone and [3H]corticosterone) of a transcortin-like component binding only the natural steroid. Whereas the number of sites of the former binder was not significantly altered during maturation and remained close to the adult value (276± 12 fmol/mg protein), that of the latter declined dramatically after birth and rose again after postnatal day 10. The apparent Kd, however, remained unchanged. Transfer of the [3H]dexamethasone-receptor complex to nuclei of pituitary cells from neonates 2–6 days of age was found to be 20% that of adults despite the presence of comparable concentrations of receptor sites. Mixing experiments carried o...

Effects of ethanol and acetaldehyde on the rat adrenal

Abstract: A pseudoCushing syndrome, indistinguishable from true Cushing syndrome except that it disappears with abstinence from alcohol, is known to occur in alcoholics. An animal model was used to study this syndrome in vitro, as earlier studies have shown that ethanol administration to animals increases corticosterone secretion. Such secretion appears to be the result of ethanol-induced ACTH secretion. We have examined the effects of ethanol and acetaldehyde on the production of three steroids: corticosterone, progesterone, and androstenedione in the isolated perfused rat adrenal. The adrenal glands and left kidney of rats were perfused with medium and one of the following additions: ethanol, acetaldehyde, ACTH or ACTH with either ethanol or acetaldehyde. The amount of the three steroids in the adrenal and the perfusion effluent was determined and compared to that of nonperfused adrenal glands. We found that perfusion with medium alone increased the production of each steroid (p

Concentrations of pituitary, gonadal and adrenal hormones in serum of laying and broody white rock hens (Gallus domesticus).

Abstract: Diurnal variations in circulating concentrations of LH, GH, prolactin, corticosterone, oestradiol, progesterone and testosterone were followed in laying and broody White Rock domestic fowl. Throughout the 24 h study prolactin concentrations in serum were consistently (two- to fourfold) higher in broody than in laying birds, in which the prolactin level varied with the light:darkness or ovulatory cycles. Concentrations of GH in serum tended to be lower in broody birds but in both groups were very variable and showed no obvious relationship with either the lighting or ovulatory cycles. Broodiness was also characterized by low LH and gonadal steroid levels and by the absence of preovulatory peaks in the serum concentrations of these hormones. A diurnal rhythm in corticosterone was observed in both the laying and broody birds, with high levels during the period of darkness. Corticosterone concentrations were markedly higher in the broody birds than in laying birds during most of the 24 h study. No diurnal rhythm in the blood haematocrit level was observed in either group, although the level was generally lower in broody birds. This difference, however, was insufficient to account for the lower LH and gonadal steroid levels in the broody birds. The results suggest that prolactin is involved in the initiation or maintenance of broodiness in the fowl and the possibility of an antigonadal role for the hormone is discussed.

Pharmacological evidence for a role of brain serotonin in the maintenance of plasma renin activity in unanesthetized rats.

Abstract: To determine whether serotonin is involved in the regulation of renin secretion in unanesthetized rats, plasma renin activity was measured in animals treated with the serotonin-depleting drugs p-chlorophenylalanine and 5,7-dihydroxytryptamine, with the serotonin releasing drug p-chloroamphetamine and with the serotonin agonist quipazine. Plasma corticosterone was also measured. p-Chlorophenylalanine decreased plasma renin activity and p-chlorophenylalanine plus 5-hydroxytryptophan increased plasma renin activity. Plasma renin activity was also reduced in rats that had received intraventricular 5,7-dihydroxytryptamine after pretreatment with desmethylimipramine. p-Chlorophenylalanine and 5,7-dihydroxytryptamine did not change plasma corticosterone concentration. p-Chloroamphetamine and quipazine produced dose-dependent increases in plasma renin activity and plasma corticosterone. The increase in plasma renin activity produce by quipazine was more rapid than that produced by p-chloroamphetamine. The effects of p-chloroamphetamine on plasma renin activity and plasma corticosterone were prevented by prior administration of p-chlorophenylalanine. The renin stimulating effect of p-chloroamphetamine was unaffected by adrenalectomy. L-Tryptophan failed to increase plasma renin activity. The data support the hypothesis that in rats release of serotonin within the central nervous system increases renin secretion and corticosterone secretion and that the increase in renin is independent of the increase in corticosterone.

Naloxone Has a Direct Effect on the Adrenal Cortex

Abstract: The effects of naloxone on basal and ACTHstimulated corticosterone secretion from superfused rat adrenocortical tissue were investigated. High doses (10-3 and 10-4M) of naloxone produced a decline in basal steroidogenesis, whereas lower doses (10-5-10-7 M) of naloxone resulted in elevations of corticosterone secretion. The simultaneous addition of an aliquot of ACTH and varying amounts of naloxone resulted in a dose-dependent alteration in the steroidgenic response by the tissue to ACTH. With higher doses (10-3 and 10-4 M) of naloxone, there were little or no significant alterations in the response to an initial dose of ACTH; however, the steroidogenic responses to ACTH administered 2 and 4 h after the single aliquot of naloxone were significantly potentiated. The lower dose of naloxone (10-610-10 M) resulted only in the potentiation of the initial ACTH response. The simultaneous administration of ACTH and 10-12 M naloxone resulted in no apparent alteration in the response to ACTH at any period in the stu...

Effects of beta-lipotropin and beta-lipotropin-derived peptides on aldosterone production in the rat adrenal gland

Abstract: To investigate the role of non-ACTH pituitary peptides on steroidogenesis, we studied the effects of synthetic beta-lipotropin, beta-melanotropin, and beta-endorphin on aldosterone and corticosterone stimulation using rat adrenal collagenase-dispersed capsular and decapsular cells. beta-lipotropin induced a significant aldosterone stimulation in a dose-dependent fashion (10 nM-1 muM). beta-endorphin, which is the carboxyterminal fragment of beta-lipotropin, did not stimulate aldosterone production at the doses used (3 nM-6 muM). beta-melanotropin, which is the middle fragment of beta-lipotropin, showed comparable effects on aldosterone stimulation. beta-lipotropin and beta-melanotropin did not affect corticosterone production in decapsular cells. Although ACTH(1-24) caused a significant increase in cyclic AMP production in capsular cells in a dose-dependent fashion (1 nM-1 muM), beta-lipotropin and beta-melanotropin did not induce an increase in cyclic AMP production at the doses used (1 nM-1 muM). The beta-melanotropin analogue (glycine[Gly](10)-beta-melanotropin) inhibited aldosterone production induced by beta-lipotropin or beta-melanotropin, but did not inhibit aldosterone production induced by ACTH(1-24) or angiotensin II. Corticotropin-inhibiting peptide (ACTH(7-38)) inhibited not only ACTH(1-24) action but also beta-lipotropin or beta-melanotropin action; however it did not affect angiotensin II-induced aldosterone production. (saralasin [Sar](1); alanine [Ala](8))-Angiotensin II inhibited the actions of beta-lipotropin and beta-melanotropin as well as angiotensin II. These results indicate that (a) beta-lipotropin and beta-melanotropin cause a significant stimulation of aldosterone production in capsular cells, (b) beta-lipotropin and beta-melanotropin have a preferential effect on zona glomerulosa cells, (c) beta-melanotropin contains the active peptide core necessary for aldosterone stimulation, (d) the effects of these peptides on aldosterone production may be independent of cyclic AMP, and (e) the receptors for beta-lipotropin or beta-melanotropin may be different from those for ACTH or angiotensin II.

Uptake and binding of [3H]aldosterone by the anterior pituitary and brain regions in adrenalectomized rats.

Abstract: The uptake of [3H]-aldosterone by the brain and anterior pituitary (AP) was studied after i.v. injection of the isotope into adrenalectomized rats. The AP showed the higher uptake ratio (i.e., radioactivity in tissue/radioactivity in blood), while the brain regions examined (hippocampus, hypothalamus, amygdala, cerebellum and cortex) contained lower levels of radioactivity, although they concentrated the hormone from blood. Neither [3H]-corticosterone nor [3H]-18-hydroxydeoxycorticosterone accumulated in the AP as much as [3H]-aldosterone, while [3H]-corticosterone's uptake was greatest in the hippocampus. Competition experiments demonstrated that [3H]-aldosterone uptake in the AP was inhibited by pretreatment of animals with excess aldosterone, corticosterone and dexamethasone, whereas aldosterone and corticosterone but not dexamethasone competed in the brain regions. Binding sites were demonstrated in vitro in cytosol fractions from AP and several brain regions. Scatchard plot analysis demonstrated high affinity, low capacity binding sites in cytosol from AP and hippocampus. These results suggest the AP and brain areas may be considered as targets for aldosterone, although the functions of the mineralocorticoid in these tissues are a matter of speculation.