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Effect of adrenalectomy on the slimming activity of liposome-carried oleoyl-estrone in the rat.

OBJECTIVE: To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoylestrone. DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 micromol/kg/d oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. SUBJECTS: Sham-operated control and adrenalectomized lean Zucker rats. MEASUREMENTS: Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen. RESULTS: Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin and leptin. Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves. CONCLUSION: The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen- and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance.

Adrenalectomy↗

Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat.

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.

Acetyl-CoA Carboxylase↗

Alpha 1- and beta-adrenergic receptors in brown adipose tissue of lean (Fa/?) and obese (fa/fa) Zucker rats. Effects of cold-acclimation, sucrose feeding and adrenalectomy.

1. The populations of alpha 1- and beta-adrenergic receptors in brown adipose tissue (BAT) of genetically obese Zucker rats (fa/fa) were studied with [3H]prazosin and [3H]CGP-12177 respectively. 2. The density of alpha 1-adrenergic receptors in BAT was significantly lower in obese than in lean Zucker rats, both at 2-4 months of age and at 6 weeks of age. The density of beta-adrenergic receptors was identical in BAT of lean and obese 6-week-old Zucker rats. 3. Cold-acclimation increased the alpha 1-receptor density significantly in BAT of both lean and obese Zucker rats, and the number of beta-receptors was also somewhat increased. 4. Sucrose feeding did not affect the density of alpha 1-receptors in BAT of lean or obese Zucker rats, but it increased beta-receptor density. 5. Adrenalectomy restored the density of alpha 1-adrenergic receptors in BAT of obese Zucker rats to the value observed in lean rats. 6. It is concluded that there is a direct correlation between alpha 1-receptor density and tissue recruitment, and that alpha 1-receptor density is thus positively correlated with sympathetic activity. beta-Receptor density is apparently better correlated with feeding conditions.

Adipose Tissue, Brown↗

Transport in isolated rat hepatocytes of the phospho-oligosaccharide that mimics insulin action. Effects of adrenalectomy and glucocorticoid treatment.

The addition to intact cells of an inositol phospho-oligosaccharide (POS), which is the polar head-group of an insulin-sensitive glycosylphosphatidylinositol, mimics and may mediate some of the biological effects of this hormone. Here we report the existence of a POS transport system in hepatocytes. This POS transport system is specific and time- and dose-dependent. Insulin-resistance caused by dexamethasone administration to rats was accompanied by a decrease in the hepatocyte POS transport system. In contrast, bilateral adrenalectomy provoked a significant increase in the transport of POS. Both the temporal uptake of POS and the regulation of this process by conditions known to modify the sensitivity to insulin suggest that this novel transport system might be involved in the insulin signalling mechanism.

Adrenalectomy↗

Procolipase mRNA: tissue localization and effects of diet and adrenalectomy.

Northern blot analysis has identified procolipase mRNA in rat pancreas, stomach and duodenum. Pancreatic colipase mRNA was increased by high-fat diets. Adrenalectomy increased pancreatic procolipase mRNA, an effect enhanced by high-fat diets. The results suggest that colipase is not unique to the pancreas and that diet and glucocorticoids interact in regulating the transcription of its gene.

Actins↗

Changes in vascular smooth muscle sensitivity to vasoconstrictor agents induced by corticosteroids, adrenalectomy and differing salt intake in rats.

1. Isolated hind limbs of rats were perfused and vascular smooth muscle sensitivity to noradrenaline, methoxamine and potassium chloride was measured and dose-response curves were obtained. 2. The sensitivity of vascular smooth muscle to noradrenaline is attenuated by adrenalectomy and low sodium diet; it is enhanced by corticosterone. High sodium diet or administration of deoxycorticosterone did not alter the dose-response curve significantly. 3. The increased sensitivity of vascular smooth muscle after corticosterone treatment is not related to changes in the contractile protein or alterations in the neuronal uptake and extraneuronal metabolism of noradrenaline. 4. These results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.

Adrenal Cortex Hormones↗

Urinary kallikrein response to repeated frusemide injections in rats: effect of adrenalectomy and deoxycorticosterone acetate treatment.

The effect of repeated intravenous injections of frusemide (0.17 mg/kg) on the urinary kallikrein excretion of normal, adrenalectomized and deoxycorticosterone acetate (DOCA)-treated adrenalectomized rats was studied. Adrenalectomy decreased baseline urinary kallikrein excretion, while DOCA treatment restored it to normal. Frusemide injections repeatedly increased urinary kallikrein excretion in the three groups of rats studied. Compared with control and DOCA-treated animals, adrenalectomized rats were less responsive. The excretion of urinary kallikrein was positively correlated with urine volume and with the excretion of sodium and potassium in all groups. The regression lines were shifted to the left in DOCA-treated adrenalectomized rats showing that mineralocorticoids enhance the effect of frusemide on urinary kallikrein excretion. The regression lines between urinary kallikrein excretion and the measured variables in adrenalectomized rats did not differ from those of control animals. We conclude that the response of urinary kallikrein to frusemide is influenced by the level of mineralocorticoid activity. The effect of frusemide on urinary kallikrein excretion does not appear to be a 'wash-out' of the enzyme since its influence did not subside after repeated injections.

Adrenalectomy↗

Adrenalectomy reduces the ability of newborn rats to gasp and survive anoxia.

The ventilatory response to anoxia in unanaesthetized rat pups of 1 and 8 days of age was studied. Ventilation was recorded by barometric plethysmography. During acute anoxia (100% N2), animals of both ages responded with hyperpnoea, primary apnoea, hypoxic gasping and secondary apnoea. After secondary gasping, occasional gasps occurred. If oxygen was administered during the gasping period, all animals survived through autoresuscitation. The duration of the period of hypoxic gasping was significantly longer in the 1-day-old animals. Adrenalectomy reduced the length of this period in both 1- and 8-day-old animals. In a second series of experiments, the effect of adrenergic antagonists on autoresuscitation was examined. Pretreatment with the non-selective alpha-receptor antagonist phentolamine reduced the duration of gasping in 1-day-old rats, but prolonged this duration in 8-day-old rats. The non-selective beta-receptor antagonist propranolol did not affect the duration of gasping in 1-day-old rats, whereas it prolonged this period in the older animals. We conclude that proper duration of gasping during anoxia is dependent on intact adrenal function and that the adrenal glands therefore play an important role in autoresuscitation from anoxia during postnatal life. The underlying mechanism appears to involve alpha-adrenergic receptors.

Adrenalectomy↗

The use of remifentanil in the anaesthetic management of patients undergoing adrenalectomy: a report of three cases.

The use of remifentanil has been recommended because of its ability to minimise the hypertensive response to tracheal intubation and surgical stimulation in various types of surgery. We describe the use of remifentanil in the anaesthetic management of three cases of open adrenalectomy, two for removal of a phaeochromocytoma and one for removal of an adrenal cortical tumour. Although the use of remifentanil was associated with no adverse events in the patient undergoing resection of the adrenal cortical tumour, its administration was associated with significant hypotension and bradycardia in the two phaeochromocytoma patients, who had both been given alpha- and beta-adrenergic receptor blocking drugs before surgery. It did not prevent the increases in blood pressure or plasma catecholamine levels associated with tumour manipulation in these patients. Remifentanil should therefore be used with caution in patients receiving alpha- and beta-adrenergic receptor blocking drugs. The use of potent vasodilators may still be necessary during tumour manipulation even if remifentanil is being infused.

Adrenal Cortex Neoplasms↗

Adrenal surgery before and after the introduction of laparoscopic adrenalectomy.

BACKGROUND: The widespread introduction of laparoscopic adrenalectomy (LA) may have broadened the indications for a surgical approach to adrenal lesions. The aim of this study was to evaluate how the introduction of the laparoscopic technique changed the profile of patients referred for adrenal surgery. METHODS: Some 243 patients, who underwent adrenal surgery between November 1986 and December 1999, were divided in two groups: patients in group 1 underwent surgery before the introduction of LA (November 1986 to May 1993) and those in group 2 were operated on after the introduction of LA (June 1993 to December 1999). The groups were compared with respect to gender, age, preoperative diagnosis and lesion size. RESULTS: There were 88 patients in group 1 and 155 in group 2. The mean number of adrenal operations per month was 1.1 during the first period and 2.0 during the second. No differences were found in gender and lesion size. The statistical analysis showed a significant difference in indications for surgery (P = 0.005). The patients in group 2 were older but, after excluding those with metastases, the difference between the two groups was not significant. CONCLUSION: The introduction of LA resulted in an increase in the number of patients referred. The criteria for patient selection did not change, but more patients with adrenal metastases and incidentaloma were operated on laparoscopically.

Adolescent↗

Adrenalectomy enhances response of tumour necrosis factor-alpha (TNF-alpha) to haemorrhage in the conscious rat.

Several factors have been implicated in TNF-alpha induction after haemorrhage, but the precise mechanism is unknown. To assess a possible role of adrenal glands on TNF-alpha induction after haemorrhage, adrenalectomized (ADX) and sham-adrenalectomized (Sham) rats were subjected to 20 ml/kg haemorrhage (approximately 30% of the total blood volume) over 5 min in the conscious state, and changes in serum TNF and hepatic TNF-alpha mRNA were analysed by cytotoxicity against L929 cells and by semiquantitative reverse transcription-polymerase chain reaction, respectively. Changes in plasma corticosterone (CS) and mean arterial blood pressure (MABP) were also detected. Plasma CS levels showed a rapid increase after haemorrhage in Sham rats, whereas there was no response in ADX rats. Responses of MABP were comparable in the two groups. Both serum TNF and hepatic TNF-alpha mRNA showed rapid increases after haemorrhage in the Sham group, and these increases were significantly augmented in the ADX group. Pretreatment with CS (100 microg/h) negated these augmentations in ADX rats. These results show that adrenalectomy enhances the response of TNF-alpha to 20 ml/kg haemorrhage in the conscious rat, and suggest that endogenous glucocorticoids may play an inhibitory role in the induction of TNF-alpha after haemorrhage.

Adrenalectomy↗

Hypophysiotropic CRF neurons display a sustained immediate-early gene response to chronic stress but not to adrenalectomy.

Immediate-early genes (IEGs) are now widely used to identify neurons acutely activated by extracellular stimuli. Though challenge-induced IEG expression is typically transient, examples of sustained elevation have been reported, including in hypothalamic magnocellular neurosecretory neurons of osmotically challenged rats. Another chronic stimulus, adrenalectomy (ADX), targets parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus (PVH), resulting in a persistent elevation in the synthesis and secretion of corticotropin-releasing factor (CRF). In the present study we used hybridization histochemical methods to compare the effects of ADX on the induction over time of two independent IEG markers, c-fos and NGFI-B, in hypophysiotropic CRF neurons. The induction of both c-fos and NGFI-B mRNA was greatest 3 to 6 after ADX, diminished by 12 h, and no longer detectable at 24, 48, 72 h, or 6 days after surgery. Immunohistochemical analyses using a Fos-specific N-terminally directed antiserum also revealed Fos immunoreactivity (-ir) in the PVH at early time points (3 h), but not later than 12 h after ADX. Combined immuno- and hybridization histochemistry on tissue from 3 h ADX rats localized Fos-ir and NGFI-B mRNA to parvocellular CRF-expressing neurons, the majority of which expressed both Fos and NGFI-B. These early IEG responses, however, were not paralleled by increases in CRF mRNA, which was not significantly elevated until 48 h after ADX. In the chronically ADX rat, CRF neurons are capable of c-fos expression since animals subjected to an acute injection of hypertonic saline 5 days after ADX displayed a robust induction of Fos-ir in the parvocellular PVH. Furthermore, a chronic challenge, insulin-induced hypoglycemia, provoked comparable c-fos mRNA and protein expression in CRF neurons in the PVH of ADX and sham-operated rats, which was observed both acutely (2 h) and chronically (5 days) after the onset of hypoglycemia. The maintenance of Fos expression in parvocellular CRF neurons following chronic hypoglycemia, but not ADX, suggests an involvement of distinct signaling pathways in the maintenance of hypophysiotropic neuron responses to chronic steroid withdrawal and stress.

Adrenalectomy↗

Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment.

We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 microm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis--identified as classical apoptotic bodies--is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60-70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.

Adrenalectomy↗

Axons containing the growth associated protein GAP-43 specifically target rat corticotrophs following adrenalectomy.

An extensive network of nerve fibers immunoreactive for the neuronal growth associated protein GAP-43 (GAP-43-IR) is present within the anterior pituitary (AP) of the rat, and the density of these fibers has been reported to increase 4 days after adrenalectomy (ADX). In the present study, we employed confocal dual-label immunofluorescence microscopy to determine whether GAP-43-IR fibers are specifically associated with corticotrophs at various intervals after ADX. A dramatic increase in the density of GAP-43-IR was apparent 4 days after ADX, and this increase was sustained at 7 and 14 days post-ADX. The percentage of corticotrophs in apparent contact with GAP-43-IR axons was 87% at 4 days after ADX and 92% at 14 days. In addition, fewer than 15% of GAP-43-IR terminals were associated with cells other than corticotrophs in either group. This highly specific targeting of corticotrophs during a period in which these cells are undergoing both hypertrophy and hyperplasia indicates that axonal sprouting is occurring in response to ADX. While the less intense GAP-43-IR in the AP of intact rats precluded precise quantitative analysis, the majority of corticotrophs also appeared to be selectively innervated in these animals. The observations that GAP-43-IR axons selectively contact corticotrophs, and that both the specificity and thoroughness of innervation are maintained by targeted growth of GAP-43-IR axons following ADX, strongly suggest that these fibers are of functional significance.

Adrenalectomy↗

Effect of corticosteroid treatment in vitro on adrenalectomy-induced impairment of synaptic transmission in the rat dentate gyrus.

Removal of the rat adrenals results after 3 days in the appearance of apoptotic cells in the dentate gyrus. Apoptosis is accompanied by an impaired synaptic transmission in the dentate gyrus. Substitution in vivo with a low dose of corticosterone was found to prevent both the appearance of apoptotic cells and the functional impairment. In the present study we determined whether the functional normalisation after corticosterone treatment critically depends on prevention of apoptosis. To address this question, brain slices from rats showing apoptosis after adrenalectomy were treated in vitro with the mineralocorticoid aldosterone (3 nM) or with 30 nM corticosterone, which is assumed to activate both mineralo- and glucocorticoid receptors. Steroids were briefly applied either during recording (acute effects) or several hours before recording (long-term effects). While the slope of the fEPSP recorded in the outer molecular layer of the dentate gyrus in response to perforant path stimulation was not affected up to 1 h after acute administration of the steroids, fEPSP slopes recorded 2.5-3 h after corticosterone or aldosterone treatment were significantly increased, to the level of the sham-operated controls. The results indicate that delayed corticosteroid effects through in vitro activation of mineralocorticoid receptors (MRs) are sufficient to normalise synaptic transmission in the dentate gyrus of ADX rats, even in the presence of apoptotic cells. We tentatively conclude that the impaired synaptic transmission seen after ADX is probably not primarily caused by the appearance of apoptotic cells.

Adrenal Cortex Hormones↗

Effects of adrenalectomy and of mineralocorticoid receptor/glucocorticoid receptor ligands in female Brown Norway and Fischer 344 rats and f1 hybrids.

Our previous studies suggested that the mineralocorticoid receptor (MR) of Brown Norway (BN) male rats is active independently of the presence of its ligands (i.e. constitutively active), and that glucocorticoid receptor (GR)-mediated mechanisms are more efficient in BN than in Fischer 344 (F344) male rats. Such functional differences in corticosteroid receptors led us to compare the effect of adrenalectomy (ADX) and MR/GR-mediated actions (treatments with deoxycorticosterone, DOC and RU 28362, respectively) on female rats from both strains, and, within the framework of a genetic study, to investigate how these differences were inherited in rats of the first generation (F1) born from the crossbreeding between BN and F344 inbred rats. This study extends our previous hypotheses of a constitutive activation of MR and of a greater efficiency of GR in males to females of the BN strain. In both strains, female rats were less sensitive to ADX and to treatments with DOC or RU 28362 than males. Globally, F1 hybrid BNxF344 rats inherited the functional characteristics of MR and GR of BN rats.

Adrenal Glands↗

Annexin-1 (lipocortin-1)-immunoreactivity in the folliculo-stellate cells of rat anterior pituitary: the effect of adrenalectomy and corticosterone treatment on its subcellular distribution.

In the pituitary gland, annexin-1 (lipocortin-1) located in folliculo-stellate (FS) cells has been advocated as one of the candidates for paracrine agents produced by FS cells that modulate the release of pituitary hormones. However, the expression and distribution pattern of annexin-1 in FS cells under different circulating corticosteroid conditions has not been examined. Thus, by means of pre-embedding immunoelectron microscopy, we investigated the expression of annexin-1 in FS cells under different corticosteroid conditions. Annexin-1-immunoreactivity was observed in the cytoplasm; especially intense immunoreactivity was detected in the follicle surface of FS cells under control conditions. After adrenalectomy, annexin-1-immunoreactivity almost disappeared, but the immunoreactivity recovered with corticosterone replacement. The expression of glucocorticoid receptor immunoreactivity in the nucleus of FS cells also showed a similar pattern to annexin-1 associated with the changes in the corticosteroid conditions. However, S-100 immunoreactivity, a marker for FS cells, was not changed whatever the corticosteroid conditions. These results confirm that glucocorticoids regulate the annexin-1 expression and demonstrate the translocation of annexin-1 from intracellular to pericellular sites in the FS cells of the rat anterior pituitary gland.

Adrenalectomy↗