Effects of prepubertal corticosterone treatment on urinary bladder

PURPOSE: The aim of this work was to analyze the bladder wall modifications after a chronic treatment with high doses of corticosterone in prepubertal rats. METHODS: This study included 26 male rats assigned into four groups: T30 was treated with corticosterone until 29 days of age and killed at day 30, while T65 group received the same treatment but was killed at day 65. Each group had its own control group (C30 and C65). For treated animals, daily intraperitoneal injections of corticosterone (20 mg/Kg) were administered between 7th and 29th day of life. Bladders were removed and collagen, smooth muscle, elastic fibers system, vascular density and epithelium were analyzed by morphometrical methods, immunofluorescence, and biochemistry. RESULTS: Vascular density in lamina propria was reduced by 40% (p<0.05) in group T65. Collagen organization was altered in T30 and T65, although total collagen concentration was unchanged. The T65 group had an increase in elastic system fibers. There was no difference in epithelial height and cell density between the groups. Concerning the smooth muscle fibers density we observed a 19% increase (p<0.05) in the T65 group. CONCLUSION: Prepubertal administration of corticosterone induces structural modifications in the bladder of rats in a medium term analysis. .

Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.

Estrogen modulates transactivations of SXR-mediated liver X receptor response element and CAR-mediated phenobarbital response element in HepG2 cells

The nuclear receptors, steroid and xenobiotic receptor (SXR) and constitutive androstane receptor (CAR) play important functions in mediating lipid and drug metabolism in the liver. The present study demonstrates modulatory actions of estrogen in transactivations of SXR-mediated liver X receptor response element (LXRE) and CAR-mediated phenobarbital response element (PBRU). When human estrogen receptor (hERalpha) and SXR were exogenously expressed, treatment with either rifampicin or corticosterone promoted significantly the SXR-mediated transactivation of LXRE reporter gene in HepG2. However, combined treatment with estrogen plus either rifampicin or corticosterone resulted in less than 50% of the mean values of the transactivation by rifampicin or corticosterone alone. Thus, it is suggested that estrogen may repress the SXR-mediated transactivation of LXRE via functional cross-talk between ER and SXR. The CAR-mediated transactivation of PBRU was stimulated by hERalpha in the absence of estrogen. However, the potentiation by CAR agonist, TCPOBOP, was significantly repressed by moxestrol in the presence of ER. Thus, ER may play both stimulatory and inhibitory roles in modulating CAR-mediated transactivation of PBRU depending on the presence of their ligands. In summary, this study demonstrates that estrogen modulates transcriptional activity of SXR and CAR in mediating transactivation of LXRE and PBRU, respectively, of the nuclear receptor target genes through functional cross-talk between ER and the corresponding nuclear receptors.

Effects of steroid hormones on total brain Na(+)-k+ ATPase activity in Oreochromis mossambicus.

The effects of administration of cortisol, corticosterone, testosterone, progesterone and a synthetic estrogen. diethylstilbestrol (DES) on total brain Na(+)-K+- ATPase were investigated in tilapia, O. mossambicus. Exogenous administration of 0.125 and 0.25 microg/g body weight of glucocorticoids and 0.125, 0.25 and 0.5 microg/g body weight of DES for 5 days significantly stimulated Na+(-) K+ ATPase activity by 14-41% in the brain, while 0.5 microg/g body weight of glucocorticoids did not evoke any response on the activity of the enzyme. Progesterone (0.125 and 0.25 microg/g body weight) administration significantly decreased the enzyme activity by 21-36% and high dose (0.5 microg/g body weight) was ineffective. Testosterone exhibited a biphasic effect on Na(+)-K+ ATPase activity--a low dose stimulated by 14% while middle and high doses inhibited it by 19-24%. The results seem to be the first report on the effect of steroids on brain ATPase activity in a teleost. When 0.25microg/g body weight of actinomycin D or puromycin was administered prior to the treatment of similar doses of hormones, the inhibitors significantly inhibited the effect of the hormones by 24-52%. This clearly shows that the effect of the hormones was sensitive to the action of inhibitors suggesting a possible genomic mode of action under long-term treatment. The results suggest that cortisol, corticosterone and DES may possibly stimulate the co-transport of glucose and excitation of membrane potential while progesterone and testosterone inhibit them in the brain of O. mossambicus by regulating the activity of Na(+)-K+ ATPase.

Influence of steroid hormones on plasma proteins in freshwater tilapia Oreochromis mossambicus.

The effect of administration of cortisol, corticosterone, testosterone, progesterone and a synthetic estrogen, diethylstilbestrol on plasma proteins of tilapia (Oreochromis mossambicus) was investigated. SDS-PAGE clearly revealed the appearance of several new bands of protein, which were not present in the control plasma and were comparable to the known bands of the molecular markers. Of the different bands appeared in the steroids treated plasma, the most important ones were the presumed vitellogenin and corticotrophin binding globulin with a molecular weight of 180 and 17 kDa, respectively. Increase in protein bands in the steroid treated plasma of O. mossambicus confirmed the anabolic role of steroids in teleost.

Effect of dexamethasone and corticosterone on activity levels of ATPase, phosphomonoesterases and phosphodiesterase in liver, muscle and testis of post-hatched White Leghorn chicks.

Muscle ATPase activity did not show much change with any of the treatments, while hepatic total and Ca(2+)-Mg(2+)-ATPase activities were decreased with low dose of dexamethasone (DXM(L) and enzyme activity in general was increased with both high dose of DXM(H) and corticosterone. Total and Ca(2+)-Mg(2+)-ATPases were increased in testis of corticosterone treated chicks. Acid phosphatase activity of testis was increased with DXM(H) and decreased with DXM(L) while the enzyme activity in all the three tissues was increased with corticosterone. Muscle alkaline phosphatase activity was decreased with DXM treatments while that of testis was decreased with both DXM(H) and corticosterone treatments. Hepatic PDE activity was decreased with DXM and increased with corticosterone while muscle PDE activity was decreased under both DXM(H) and corticosterone treatments. The results suggest that both hypo. and hypercorticalism can induce tissue specific differential alterations in phosphomonoesterases, ATPases and PDE during early phases of post-natal development of chicks.

Effects of chronic treatments with adrenal steroids on acid-base homeostasis in the rat

Urinary parameters related to acid base homeostasis were studied in adrenalectomized rats (ADX) as well as in ADX treated with physiological doses of corticosterone (B), aldosterone (aldo) or 18-Hydroxycorticosterone (l8HOB) during 1,3 or 5 days, under basal conditions and after gravage with 200 mM HCI. The results showed: a) a persistent effect of B and l8HOB increasing titratable acidity principally in response to acidosis; b) an increased phosphate elimination in acidotic B treated ADX on the first day, and in 18 HOB treated ADX on days 3 and 5; c) pronounced increases in blood pH and blood bicarbonate levels provoked by the three steroids on day 1; d) increments of ammonium elimination in response to acidosis by aldo treatmets on the first day, while B and l8HOB increase ammonium elimination under almost all conditions during the whole experiment; e) the effects of B and 18 HOB would be independent of an increase in sodium retention as well as glomerular filtration rate.

Effect of exogenous dexamethasone and corticosterone on weight gain and organ growth in post-hatched white Leghorn chicks.

Induced chronic hypocorticalism by dexamethasone (DXM) and hypercorticalism by corticosterone (CORT) retarded body weight gain as well as the growth of spleen, bursa, liver, kidney and pancreas during the first month of development in male leghorn chicks. Adrenal weight was reduced by DXM and increased by CORT. Correspondingly, there were histological regressive changes in the cortex with a decreased cortico-medullary ratio with DXM treatment, while a reverse trend was there with CORT treatment. However, an increase in weight of testis and better organization of seminiferous cords and interstitium was observed in DXM treated chicks, and there was a decrease in weight and poor histological organization in CORT treated chicks. Both DXM and CORT induced stimulatory changes in thyroid denoted by increased epithelial cell height and decreased colloidal content. These observations indicate that corticosteroids have definite influence on post-hatched growth and maturation of chicks.

Involvement of dietary glucose in adrenal steroidal regulation of spermatogenic and steroidogenic activities in prepubertal rat testis.

Effects of dietary and supplemented dextrose energy on the role of corticosterone (Comp. B) or dehydroepiandrosterone (DHA) in spermatogenic and steroidogenic activity in the bilaterally adrenalectomised prepubertal rat testis were studied. Adrenalectomy reduced the body and testis weight, numbers of the stage VII cell types [spermatogonia A (A), preleptotene (PL) and pachytene (P) spermatocytes and step 7 spermatid (7)], testicular delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-OH-SDH) activity and serum testosterone. Adrenalectomy also caused reduction of energy intake due to loss of appetite which was stimulated by hormone replacement therapy. Treatment of adrenalectomised rats with DNA or corticosterone enhanced the spermatocyte population and the enzyme activity, especially after 30 days of age. Dextrose supplementation with hormone treatment however, did not produce significant additive effect on stage VII cell counts, but delta 5-3 beta-OH-SDH activity showed additive effect in this age group. Results suggest that adrenal steroids regulate testicular steroidogenesis and spermatogenesis during the prepubertal ages by modifying the supply of dietary glucose.

Corticosterone administration and lipid metabolism in brain regions during development.

Effect of corticosterone on lipid contents of different brain regions and the effect of age on the sensitivity of these regions to corticosterone have been studied. Corticosterone administration (40 mg/kg body wt, sc) to 17-day-old rat for 3 days led to significant decrease in phospholipid content of cerebellum and increase in cholesterol contents of hippocampus and striatum. However, there was no effect on cerebral cortex and brain stem lipids. This alteration in lipids was associated with decrease in [U-14C] glucose incorporation into cholesterol and phospholipids, decrease in plasma beta-hydroxy butyrate levels and increase in beta-hydroxy butyrate dehydrogenase activity in hippocampus and striatum, thereby suggesting that suppression of glucose utilization by corticosterone was compensated by higher utilization of ketone bodies for lipid synthesis in these regions. The sensitivity to corticosterone appears to be age-specific as, at 20-day, cerebellum, hippocampus and striatum were susceptible, at 10-day only hippocampus and at 40- and 90-day none of these regions responded to the treatment.

Effects of withdrawal of glucocorticoids on improving the function and enzymatic activities of liver mitochondria in female diabetic rats

En el presente trabajo se describen los efectos de la restitución de corticosterona a ratas con diabetes inducida por estreptozotocina sobre a) la función de mitocondrias enteras de hígado y b) sobre las actividades enzimáticas de la 3- hidroxibutirato deshidrogenasa (HBD), citocromo c oxidasa (Cox) y succinato deshidrogenasa (SD) de mitocondrias que sufrieron ruptura por método físico. La función mitocondrial fue analizadas por la respiración y por el comportamiento oscilatorio osmótico de esas organelas. La respiración se midió por método polarográfico y se midieron el estado 3 de la respiración activa (S3) y el control respiratorio (CR) usando los siguientes sustratos: 3-hidroxibutirato, malato-glutamato y succinato. El comportamiento oscilatorio osmótico se midió usando como parámetro comparativo los coeficientes de amortiguación (CA), que son los cocientes de las amplitudes de dos picos o valles consecutivos obtenidos en el registro espectrofotométrico de dicho fenómeno. Se dispusieron un grupo de ratas normales no diabéticas (N) y los siguientes grupos de ratas diabéticas: controles (D), adrenalectomizadas (D + ADX) y adrenalectomizadas con restitución de corticosterona (D + ADX + C). Los resultados de la respiración mitocondrial mostraron que los valores medios de S3 y CR disminuyeron con los tres sustratos en el grupo D + ADX + C comparado con el grupo D + ADX (p < 0,001). Este grupo demostró, a su vez, un aumento significativo de los valores medios de S3 y CR de respiración con respecto al del grupo D. El comportamiento oscilatorio de mitocondrias enteras de hígado del grupo D + ADX + C demostró un significativo aumento de los CA de picos y valles comparado con los del grupo D + ADX. Los valores de CA del último grupo no fueron significativamente diferentes de los del grupo N. El comportamiento de las actividades enzimáticas de mitocondrias fraccionadas fueron diferentes para cada enzima según los diferentes tratamientos en los grupos de ratas diabéticas. En el grupo D + ADX + C el valor medio de la actividad HBD disminuyó significativamente, el de la Cox aumentó (p < 0,02) y el de la SD no mostró variación alguna con respecto a los correspondientes valores medidos de esas enzimas en el grupo D + ADX. Asimismo, el valor medio de la actividad HBD en este último grupo fue similar al del grupo N y el de Cox fue menor (p < 0,001) que el del grupo D. Se concluye que la corticosterona tiene un significativo efecto diabetogénico sobre la función bioquími

Adrenocortical influence on histokinetics and lipid components of uropygial gland of immature chick.

Adrenocortical influence on uropygial gland of 10-day old male white leghorn chicken was assessed by suppressing glucocorticoid level with metyrapone and following corticosterone and deoxycorticosterone acetate (DOC) treatments (im), 100 micrograms each on alternate day for a period of 15 days. Metyrapone treatment resulted in significant atrophy of the uropygial gland with a severe regression of the glandular alveoli due to cytopycnosis, cellular disintegration and drastic cell loss. Concomitantly, there was a depletion of glandular lipid and its diester wax fraction. Corticosterone, administered simultaneously with metyrapone, counteracted severe adverse effects of the latter on the uropygial gland. In the normal chicken also corticosterone alone caused glandular hypertrophy with increased rate of cell renewal and cell growth within the alveoli and, to a lesser extent, augmented output of the glandular lipids. Simultaneous administration of corticosterone and testosterone propionate (TP), on the other hand, caused a moderate suppressive influence on this gland. DOC treatment alone or with metyrapone and TP failed to exert any noteworthy change in the uropygial gland excepting a moderate reduction of gland weight and a rise of glandular lipids observed after combined injections of DOC with TP and with metyrapone respectively.

Effects of thyroidal, gonadal and adrenal hormones on tissue respiration of streaked frog, Rana limnocharis, at low temperature.

In vivo and in vitro effects of thyroidal, gonadal and adrenal hormones were studied on the rate of liver and skeletal muscle respiration in both the sexes of R. limnocharis during active and inactive phases of the annual activity cycle. Triiodothyronine (L-T3) and thyroxine (L-T4) did not stimulate tissue (liver and muscle) respiration in any of the experiments irrespective of season, sex and temperature. Testosterone, estradiol and corticosterone stimulated O2 uptake significantly irrespective of season, sex and temperature. Adrenaline and nor-adrenaline also stimulated tissue respiration significantly during the winter month. Since the ambient temperature was low even during the active phase (max. temperature 21 degrees C), it seems that the frog might have developed tissue sensitivity for gonadal and adrenal hormones at low temperatures when thyroid hormones are calorigenically ineffective.

Açäo da corticosterona sobre a secreçäo de insulina / Action of the corticosterone upon insulin secrection

Esta revisäo discute a açäo da corticosterona na secreçäo de insulina. A açäo da corticosterona depende da abordagem metodológica, a administraçäo prolongada do esteróide provoca, em vários animais hiperglicemia e hiperinsulinemia, enquanto que uma simples dose de corticosterona, acompanhada de uma injeçäo de glucose promove uma queda nos níveis de insulina sérica. Em ilhotas pancreáticas isoladas, a corticosterona inibe a secreçäo de insulina, induzida por glucose, aminoácidos, cetoácidos e sulfonilureas. O efeito inibidor é direto e imediato, e está associadao ao fluxo de cálcio. A célula B pancreática pode, desta forma servir como modelo para estudos sobre a açäo imediata de compostos esteróidais

Effect of corticosteroids on electrolyte transport in the descending colon of the rat

El efecto de corticosteroides sobre el movimiento de electrolitos fue estudiado en un modelo de saco evertido del colón distal de rata. La corticosterona tiene un significativo efecto estimulador, dependiente de la dosis, sobre la transferencia de sodio y líquido. Con la baja dosis de 10-9M la corticosterona aumentó la absorción de sodio en 29.4 micronEq g-1 h-1, valor que fue estadisticamente mayor que el efecto de dexametasona 10-9M. Con la alta concentración de 10-7M el efecto de corticosterona sobre el movimiento de sodio fue dos veces el de aldosterona o dexametasona en concentraciones equimolares. En cambio, el efecto de corticosterona sobre el movimiento de potasio fue bifásico: a baja concentración (10-9M) se encontró una significativa secreción neta, mientras que con corticosterona 10-7M se observó absorción de potasio. La dexametasona aumentó significativamente la secreción neta de potasio, mientras que el efecto de aldosterona sobre el movimiento de potasio no fue significativamente diferente de los controles. Estos datos sugieron que el glucocorticoide nativo, corticosterona, ejerce un control regulatorio de la función de los electrolitos y líquidos del colon

Effect of steroid hormones and vitamin B6 on age dependent changes in aminotransferases in rat.

Experiments have been carried out on liver and Kidneys to study the age dependent changes in alanine and aspartate aminotransferases and the influence of steroid hormones corticosterone (catabolic), testosterone (anabolic) and vitamin B6 on these changes. The rats used were of the ages between 7 to 73 weeks. It is observed that specific activity of alanine aminotransferase as well as the activity per liver increased with age. The same is true with the kidneys. Corticosterone treatment brings about two and half fold increase in activity in the liver of younger rats, whereas there is only 25% increase in the oldest group. Testosterone and vitamin B6 lower this activity, the latter showed more pronounced effect. In the case of kidneys the changes are marginal. Aspartate aminotransferase shows marginal changes in the specific activities in both liver and kidney, whereas the total activity increases with age, except in the case of liver where there is decrease at 73 weeks. Both testosterone and vitamin B6 have marginal influence on the kidney enzyme. There is no apparent explanation for the differential behaviour of the two enzymes.