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Differential mood response to natural and synthetic corticosteroids after bilateral adrenalectomy: a case report.

A 48-year-old woman who had had a bilateral adrenalectomy for Cushing's syndrome developed severe psychotic symptoms that were unresponsive to psychotropic drugs as long as she was taking prednisone (PRED) as replacement therapy. However, after she was switched to a regimen of cortisol (CORT) and fludrocortone (FLUD) the psychopathology disappeared. Mechanisms related to the differences in the interaction of natural (e.g. CORT) and synthetic (e.g. PRED) corticosteroids with the central glucocorticoid and mineralocorticoid receptors may explain the different effects upon psychopathology.

Adrenalectomy↗

Brush border Mg2+-HCO-3-ATPase, supernatant carbonic anhydrase and other enzyme activities isolated from rat intestinal mucosa: effect of adrenalectomy and aldosterone administration.

The possible role of Mg2+-HCO3-ATPase, carbonic anhydrase and several other enzymes in rat intestinal mucosa as mediators of the action of aldosterone has been examined. The small-intestinal tract was cut into seven segments, 15 cm each in length and the mucosa was scraped off, homogenized in 50 mM D-mannitol-2 mM Tris-HCl buffer (pH 7.1), differentially fractionated and a crude brush border was obtained. The mucosa from the colon and rectum was combined and used as the large-intestinal sample. Five days after the adrenalectomy, activities of brush border Mg2+-HCO3-ATPase and supernatant carbonic anhydrase from the upper small intestine decreased to about 60 and 40% of normal values, respectively. Activities of Na+-K+-ATPase, beta-glycerophosphatase and succinate dehydrogenase were all decreased. Two and 4 h after i.p. injection of aldosterone (40 micrograms/kg) to adrenalectomized rats, all enzyme activities increased except for Na+-K+-ATPase in the upper small intestine. In contrast, Mg2+-HCO-3-ATPase and carbonic anhydrase activities were unchanged 3 h after i.p. injection of dexamethasone (200 micrograms and 1 mg/kg). The activation of both Mg2+-HCO3-ATPase and carbonic anhydrase by a single injection of aldosterone was blocked by pretreatment with cycloheximide (1 mg/kg). These results suggest that aldosterone may induce the synthesis of enzyme proteins in the intestinal mucosa.

Adenosine Triphosphatases↗

Response of exocrine pancreas to corticosterone and aldosterone after adrenalectomy.

The long-term effect of adrenalectomy (Adx) on the exocrine pancreas was examined in female adult rats. Pancreatic amylase concentration decrease to 50% of the control level starting 10 days after Adx, whereas the levels of trypsinogen and lipase remained unchanged. Replacement studies beginning 24 h after surgery with corticosterone (B, 1 mg/100 g body wt) or aldosterone (ALDO, 8 micrograms/100 g body wt) alone did not prevent the decline in amylase after Adx. However, when both hormones were administered together, pancreatic amylase concentration was maintained at a level similar to that of the control group. Serum corticosterone levels in the rats receiving B alone or B + ALDO were not different, and were comparable to levels found in normal rats. Both ALDO and B, given for 5 days starting 10 days after Adx, were required to restore amylase concentrations toward control values. When spironolactone (SPIRO, 3 mg/100 g body wt), a specific mineralocorticoid receptor blocker was administered bid together with ALDO + B, it blocked the increase in pancreatic amylase seen in ALDO + B treated rats but did not affect the serum corticosterone levels. These results suggest that mineralocorticoids are also involved in modulating the level of amylase in the rat exocrine pancreas.

Adrenal Glands↗

Restraint stress depresses prolactin surges in pseudopregnant rats and adrenalectomy does not alter the response.

Experiments were performed to determine whether restraint stress decreases the two prolactin (PRL) surges in pseudopregnant (PSP) rats in a manner similar to the stress-induced decrease of the proestrous PRL surge. Adrenal involvement as well as adaptation of the response was also investigated. Vaginal cycles were followed and animals exhibiting 2-3 normal cycles were cervically stimulated (CS) electromechanically to induce PSP. In one experiment the effect of adrenalectomy (ADX) on the nocturnal surge (NS) was investigated and was found to have no effect. In another set of experiments the effect of restraint stress was investigated. Immediately following an initial sample, the animals to be stressed had their hind legs tied together with plastic coated bell wire. Subsequent samples were taken for 3 hours. Restraint stress decreased the NS to 15% of the initial value within 30 minutes. ADX did not alter this response. Furthermore, 6-9 days of 3 hours of restraint stress did not attenuate the stress-induced decrease of the NS. Restraint stress also depressed the diurnal surge in PSP rats. These results indicate that restraint stress applied during the two PRL surges of PSP results in significant decreases in plasma PRL and that this response is not altered by ADX or by habituation to the stimulus.

Adrenalectomy↗

Adrenalectomy increases beta-lipotropin secretion over beta-endorphin secretion from anterior pituitary corticotrophs.

Previous studies have indicated that acute stress in vivo or ovine corticotropin releasing hormone (oCRH) in vitro, releases both beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) from the anterior lobe, with beta-END predominating over beta-LPH by 2:1. However, repeated stress shifts this ratio to proportionately more beta-LPH released with re-stress or oCRH in vitro. Alternative hypotheses were that the glucocorticoids released during stress altered the processing of proopiomelanocortin (POMC) or that the increased biosynthetic drive resulted in an inability of the processing enzymes to keep pace with biosynthesis. To distinguish between these alternatives, adrenalectomy studies were performed. Following removal of glucocorticoid negative feedback there is greatly increased secretion of beta-END-IR from anterior lobe corticotrophs with a subsequent increase in biosynthetic drive. Under these conditions of increased biosynthetic drive in the absence of steroids, the corticotroph secretes primarily beta-LPH, suggesting that increased biosynthetic drive alters the posttranslational processing rate of POMC.

Adrenal Glands↗

Fetal and maternal levels of corticosterone and ACTH after pharmacological adrenalectomy.

A paradigm of pharmacological adrenalectomy of pregnant rats and fetuses in utero is described. A regimen of twice daily metyrapone injections (10 mg/100 gm body weight), results in marked depression of serum corticosterone in pregnant and in fetal rats without surgical trauma and stress. The technique should be useful in a wide variety of studies involving the developing brain-adrenal axis.

Adrenal Glands↗

Stress-induced hypertension: effects of adrenalectomy and corticosterone replacement.

The effect of adrenalectomy on the hypotensive response induced by social deprivation was studied in a line of Wistar-derived rats. Prior removal of the adrenal gland by surgery was found to prevent the elevation in systolic or diastolic blood pressure observed in sham-operated isolated rats. The social deprivation-induced hypertensive response ran parallel with an increase in the levels of plasma corticosterone. Supplementation therapy with this glucocorticoid in previously adrenalectomized animals restored the levels of plasma corticosterone to normal and made the rats able to respond to social deprivation with an elevation in arterial pressure. Thus, corticosterone plays a "permissive" role in the elevation of blood pressure due to isolation. Apparently, this effect is dependent upon genetic, maturational and environmental factors since it is only evident in some lines of Wistar rats.

Adrenalectomy↗

Adrenalectomy potentiates the morphine--but not cocaine-induced place preference in rats.

The conditioned place preference paradigm is commonly used to study the reinforcing properties of various drugs. In the present study, the effect of adrenalectomy (ADX) on the morphine-induced place preference was examined in rats. Morphine produced a significant preference for the drug-associated place in sham-operated (sham) and ADX rats. In sham rats, only the highest dose of morphine (8 mg/kg, i.p.) produced a significant preference, while in ADX rats, lower doses of morphine (1 and 2 mg/kg, i.p.) produced a significant preference for the drug-associated place. Furthermore, the morphine-induced place preference was blocked by the dopamine D1 antagonist SCH23390 in both sham and ADX rats. On the other hand, the cocaine-induced place preference was not affected by ADX. In the present study, we found that ADX potentiates the reinforcing effect induced by morphine, but not that induced by cocaine, which suggests that the enhancement by ADX may be due to a change in opioid receptors, morphine metabolism and/or some other cause, but not a change in dopamine receptors.

Adrenalectomy↗

Effect of adrenalectomy on the metabolism of glucose in obese (C57 Bl/6J ob/ob) mice.

The genetically obese mouse, C57 B1/6J ob/ob, has been suggested as an appropriate model for the study of obesity associated with diabetes mellitus. Employing glucose 14C(microliter) as a tracer, the data presented here indicate that obese mice are able to clear glucose from the blood compartment at the same rate as their lean littermates. This was demonstrated with or without an associated cold glucose load. The abnormal glucose tolerance curves observed in the obese animals may be a result of secretion of glucose into the blood. Removal of the adrenal glands from the obese mice and their lean littermate does not impair their ability to clear a glucose load from the vascular compartment. The capacity for endogenous glucose secretion of ob/ob mice is severely curtailed by adrenalectomy, in that the glucose tolerance curves of these adrenalectomized animals become similar to those of sham-operated lean littermates. Thus, it appears that a considerable component of the hyperglycemia in ob/ob mice reflects major adrenal involvement that is activated by stress, ie, ether anesthesia and blood sampling. The hyperglycemia in ob/ob mice may reflect glucocorticoid-dependent gluconeogenesis.

Adrenal Glands↗

Effects of centrally-administered bombesin and adrenalectomy on behavioral thermoregulation and locomotor activity.

Bombesin is an oligopeptide which has been implicated as a possible neurotransmitter or neuromodulator in the central nervous system. Central administration of the peptide produces physiological and behavioral responses which suggest a downward shift in the set point of body temperature. These include hypothermia, decreased metabolic rate and increased behavioral responding to escape from radiant heat. Contradictory data also exist. Therefore, a series of experiments was conducted to evaluate further the effects of the central administration of bombesin on behavioral thermoregulation and general locomotor activity. It was found that microinjections of bombesin into the preoptic area of the anterior hypothalamus increased the number of behavioral responses to radiant heat. The increased responding for heat-reinforcement and heat-escape suggested an activation of general locomotor activity. This was confirmed by the finding that centrally-administered bombesin increased the number of responses to escape from radiant heat without altering the duration of exposure to heat. Additionally, bombesin had no effect on the number of heat-escape responses following adrenalectomy. It was concluded that bombesin acts within the hypothalamus to increase general locomotor activity via the sympathetic outflow to the adrenals. This behavioral excitation is apparently expressed as an increase in responding to heat, or escape from heat, independent of thermoregulatory mechanisms. Therefore, the behavioral data do not indicate that bombesin decreases the set point of body temperature.

Adrenalectomy↗

Adrenalectomy attenuates stimulation-produced analgesia.

Ablation of the adrenal glands potentiates analgesia induced by morphine and attenuates an opioid form of stress-induced analgesia. the adrenal cortex has been implicated in analgesia induced by morphine and enkephalin-like peptides in the adrenal medulla have been suggested to modulate stress-induced analgesia. The effect of adrenalectomy upon analgesia produced by stimulation of the brain has not been investigated. The present investigations demonstrated that antinociception (measured with the tail-flick test) from focal stimulation of the periaqueductal grey was attenuated or abolished after adrenal ablation. These results implicate adrenal hormones in the regulation of the endogenous pain inhibitory system in the brain.

Adrenalectomy↗

The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT).

The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT was significantly greater in female compared with male rats. Adrenalectomy in male rats enhanced the hypothermic response, an effect prevented by corticosterone implants. Ovariectomy significantly attenuated the hypothermia induced by 8-OH-DPAT, an effect prevented by oestradiol-17 beta implants. Neither type of steroid manipulation affected the behavioural syndrome. These results show that sex, corticosterone and oestradiol-17 beta modulate the hypothermic response to 8-OH-DPAT in the rat, with corticosterone and oestradiol-17 beta having opposing effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Modification of prenatal stress effects in rats by adrenalectomy, dexamethasone and chlorpromazine.

This study was designed as a 4 (maternal treatments) by 2 (prenatal stress) factorial. The 4 treatment groups were: chlorpromazine (CPZ) 2.1 mg/kg; dexamethasone (DEX) 38.7 mug/kg; adrenalectomy (ADX); and controls (CON). Half of the females in each group were stressed prior to mating and during gestation. Stress significantly reduced birth and weaning weights of CON offspring but did not affect the weight of CPZ, DEX or ADX offspring. At birth, DEX and ADX offsrping, as well as offspring of partially adrenalectomized females, were significantly lighter than controls; at weaning, only the DEX animals displayed a weight deficit. Stress increased open field activity of ADX offspring but decreased the activity of DEX offspring while the performance of CON and CPZ offspring was not affected. In a food deprivation test at 42 days there were significantly more deaths among male offspring of no stress (32 percent) than of stress (4 percent) females and stress offspring in all groups lost less weight than unstressed offspring in a food deprivation test at 69 days. Avoidance conditioning tests showed effects only in female offspring. Stress significantly decreased avoidances made by CON offspring and increased avoidances made by DEX offspring. Treatment with ADX, CPZ or DEX can prevent the effects of prenatal stress on some characteristics of the offspring, but in other cases the effects are potentiated by these manipulations.

Adrenalectomy↗

Saccharin aversion in the rat following adrenalectomy.

Changes in saccharin preference as a function of concentration were studied in rats after either adrenalectomy of sham surgery. A 48 hr two-bottle preference test was used. Under two different sets of testing conditions, adrenalectomized animals rejected saccharin solutions at concentrations that were highly acceptible to controls and did not show an appetitive behavior towards andy of the concentrations tested. This aversion pattern persisted even when preference tests were conducted for as long as 10 days. However, it was abolished when the adrenalectomized rats wre exposed to saccharin for 6 days prior to surgery, or when they were administered the glucocorticoid dexamethasone. Results are discussed with respect to the effects of adrenal hormones on sensory systems and to taste-aversion learning.

Adrenalectomy↗

Prevention of adrenalectomy-induced brain growth stimulation by corticosterone treatment.

Previous research in our laboratory has shown that adrenalectomizing rats on day 11 postnatal leads to subsequent increases in brain weight, cellularity (measured in terms of DNA content), and myelination. The present study was designed to determine whether these effects are due to removal of circulating glucocorticoids. Male and female albino rats were adrenalectomized (ADX) on day 11 and then injected daily with either 7.0 mg/kg corticosterone in a steroid suspension vehicle or vehicle alone. A third group of animals was sham-operated (SHAM) and given daily vehicle injections. Subjects were sacrificed at 60 days of age for measurement of brain and body weights, cerebral DNA content, and the activity of 2',3'-cyclic nucleotide phosphodiesterase (CNP), a myelin marker enzyme. As expected from our earlier findings, brain weights and DNA and CNP levels were all significantly elevated in ADX-untreated rats compared to SHAMs. More importantly, all of these changes were completely prevented by chronic corticosterone administration. These results are consistent with previous reports that corticosterone treatment blocks increased brain growth in ADX weanling rats and support our hypothesis that the brain growth stimulating effects of day-11 adrenalectomy are likewise mediated by the removal of glucocorticoids. It appears that glucocorticoid hormones exert a tonic inhibition of at least some growth related processes in the brains of intact developing organisms.

Adrenalectomy↗

Adrenalectomy and dexamethasone differentially affect postswim antinociception in mice selectively bred for high and low stress-induced analgesia.

The effects of dexamethasone and naloxone on analgesia induced by swimming (3 min, 20 degrees C) were studied in the 6th and 7th generations of adrenalectomized and intact mice selectively bred for high (HA) and low (LA) postswim analgesia. Swim-induced analgesia in intact HA animals was significantly reduced by naloxone and dexamethasone while in LA mice these two compounds were ineffective. Naloxone ability to reverse adrenalectomy-caused swim analgesia increase was much greater in HA than in LA mice. In both intact and adrenalectomized HA animals dexamethasone and naloxone decreased postswim analgesia to the level observed in LA mice. It is suggested that selective breeding for high and low swim analgesia modified the extent of pituitary-adrenal axis involvement in the generation of stress-induced analgesia.

Adrenalectomy↗

Effects of adrenalectomy upon proceptivity, receptivity and sexual attractiveness in ovariectomized marmosets (Callithrix jacchus).

The sexual behaviour of seven pairs of marmosets was observed during blocks of 30 minute tests before and after the ovariectomized partners were bilaterally adrenalectomized. Adrenalectomized females were maintained by intramuscular injections of deoxycorticosterone pivalate (DC) and hydrocortisone hemisuccinate (HC). Twice daily injections of HC were required to maintain the high levels of plasma cortisol typical of marmosets and some other New World primates. Adrenalectomy had no significant effects upon proceptivity, receptivity or female sexual attractiveness. Increasing the replacement dose of DC had no effects upon sexual behaviour. Oestradiol treatment caused a marked increase in proceptivity (tongue-flicking, staring and immobile displays) and in receptive tongue-flicking behaviour. Males ejaculated more frequently during tests with oestradiol-treated partners. These results indicate that during "pair tests" adrenocortical sex steroids are not essential for maintenance of sexual behaviour in female marmosets and that activation of proceptivity by oestradiol 17 beta can occur in the absence of the adrenal glands.

Adrenalectomy↗

Feeding and macronutrient selection patterns in rats: adrenalectomy and chronic corticosterone replacement.

To analyze further the role of corticosterone (CORT) in the control of feeding behavior, we examined the impact of adrenalectomy (ADX) and chronic CORT implants on the food intake and macronutrient self-selection patterns of adult male rats at different periods of the diurnal cycle. Consistent with a separate study of acute CORT injection in ADX rats (Kumar and Leibowitz, 1988), the present findings indicate that ADX significantly attenuated the rats' daily (24 hr) ingestion of all three macronutrients, namely, protein, carbohydrate and fat. However, food intake in the dark cycle, specifically during the first few hours after dark onset, was significantly more affected (-70%) than feeding in the later dark and light periods (-25%). Moreover, during this early dark time when circulating CORT level normally peaks, ADX appeared to have its strongest suppressive effect on carbohydrate ingestion. Chronic subcutaneous CORT implants in the ADX animals reversed these effects of surgery and generally restored the rats' eating patterns to that of the cholesterol-implanted SHAM animals. These findings suggest that CORT exerts a decisive influence on caloric intake, on the diurnal pattern of feeding, and on appetite for specific macronutrients. The impact of CORT on carbohydrate intake is apparent specifically during the active eating period, particularly at dark onset when endogenous CORT levels normally peak and carbohydrate is exhibited as the preferred macronutrient.

Activity Cycles↗