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Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat.

The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin-releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series in situ hybridization histochemistry was used to quantify levels of eight accurate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin-releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptide Y mRNA was contained in 18% of the fluorogold-positive neurons in the arcuate, proopiomelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin-releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adrenalectomized rats.

Adrenal Glands↗

Regulation of GFAP expression in glial-like cells of the rat pituitary intermediate lobe by lactation, salt-loading, and adrenalectomy.

Glial-like cells in rat pituitary intermediate lobe were localized and characterized by immunohistochemistry with antisera against glial fibrillary acidic protein (GFAP) and S-100. Individual GFAP immunoreactive (IR) cells possessed several processes that often branched into secondary and tertiary processes, terminating with end-feet. The GFAP-immunopositive cell population was distributed in specific rostrocaudal and dorsoventral patterns. The distribution and numbers of cells differed between male and female rats. Examination of altered physiological states, e.g., adrenalectomy, lactation, and salt-loading, revealed state-specific changes in the appearance and distribution of GFAP-IR cells. Adrenalectomy and lactation increased GFAP-IR glial-like cell numbers, whereas salt-loading decreased their numbers and the typical pattern of distribution. By contrast, S-100-expressing cells were evenly distributed in male and female rats, and its expression was not affected by the experimental conditions. Double-label immunocytochemistry indicated that GFAP-IR cells are a subpopulation of S-100-IR cells. These results suggest that cells normally expressing only S-100 may be induced to express GFAP under altered physiologic conditions.

Adrenalectomy↗

Plasma insulin in response to enterostatin and effect of adrenalectomy in rats.

Enterostatin has previously been reported to alter serum insulin and corticosterone levels after central administration of the peptide. The purpose of the present study was to investigate the effect of peripheral administration of enterostatin on insulin and corticosterone levels as well as the response of plasma insulin to enterostatin administration in adrenalectomized rats. Female Sprague-Dawley rats were given a bolus injection intravenously with enterostatin alone or together with glucose. Enterostatin increased basal plasma levels of insulin, but significantly inhibited the increase in plasma insulin stimulated by glucose. Plasma corticosterone levels were not altered after a single intravenous injection of enterostatin. In rats infused chronically with enterostatin, plasma insulin levels were significantly reduced and plasma corticosterone levels were increased. The daily food intake was lower in these rats, but there was no effect on body weight. After adrenalectomy, the responsiveness of plasma insulin to enterostatin infusion was completely abolished. Furthermore, adrenalectomy itself reduced basal plasma levels of insulin and increased plasma levels of endogenous enterostatin. These results suggest that peripheral enterostatin administration produces a similar effect as central infusion of the peptide, and that the glucocorticoid hormones are involved in the regulation of plasma insulin by enterostatin.

Adrenalectomy↗

Adrenalectomy reduces adiposity by decreasing food efficiency, not direct effects on white adipose tissue.

OBJECTIVE: This study was conducted to establish the effects of adrenalectomy (ADX) on adipose tissue metabolism in male Sprague-Dawley rats fed a standard chow diet. RESEARCH METHODS AND PROCEDURES: The effects of adrenalectomy on adipose cell size, lipoprotein lipase activity, and basal and insulin-stimulated glucose conversion to lipid and lipolysis were measured. RESULTS: ADX decreased body weight gain during the post-operative period in the absence of changes in food intake; feed efficiency was decreased significantly. ADX decreased adipocyte size by 30%. ADX increased adipocyte response to the effect of submaximal concentrations of insulin on lipid synthesis and lipolysis. ADX decreased maximally insulin-stimulated lipid synthesis, but this effect was accounted for by decreased adipocyte size. In contrast, ADX had no effect on maximally insulin-inhibited lipolysis. ADX did not affect heparin-releasable LPL. The small effect of ADX on residual extractable adipose tissue LPL activity was accounted for by decreased fat cell size. DISCUSSION: ADX decreased adiposity in the absence of changes in food intake, lipoprotein lipase activity, and adipocyte lipid metabolism. The effect is best attributed to decreased feed efficiency.

Adipocytes↗

The present role of adrenalectomy in breast cancer.

Evidence does not support the argument that surgical adrenalectomy carries too great a risk to justify its use in the treatment of advanced breast cancer. The increasing availability of methods of measuring tumour receptors will undoubtedly increase the level of accuracy in predicting response to surgical adrenalectomy. The operation itself is well within the scope of most experienced general surgeons. In view of the good quality of life for those who respond well and the possibility of prolonging survival far beyond that achieved by other treatment methods, there seems to be no reason why it should not continue to be recommended on a carefully selective basis to certain women with advanced and progressive breast cancer.

Adrenalectomy↗

The effect of adrenalectomy on the restraint stressed induced suppression of MHC class II expression by murine peritoneal macrophages.

Restraint stress suppresses the expression of MHC class II (I-A) glycoproteins by murine peritoneal macrophages. In order to evaluate the role of the pituitary adrenal axis, the effect of restraint stress on I-A expression by macrophages from adrenalectomized mice was evaluated. Adrenalectomy resulted in elevated levels of ACTH but abrogated the increase in corticosterone that results from restraint stress. The expression of I-A by macrophages from adrenalectomized mice was similar to that of sham operated mice or untreated mice. Adrenalectomy ameliorated the suppressive effects of restraint but the expression of I-A was below that of macrophages from adrenalectomized control mice. These results suggest that other factors in addition to corticosterone may effect I-A expression by murine peritoneal macrophages. A survey of other neuropeptides and catecholamines indicated that the addition of ACTH or epinephrine to macrophage cultures resulted in a suppression of I-A expression.

Adrenalectomy↗

Mechanism of increased rate of de novo purine biosynthesis in rat liver after bilateral adrenalectomy.

The incorporation of [14C]glycine to hepatic purines increased proving the increased rate of de novo purine biosynthesis in rat liver after bilateral adrenalectomy in comparison to sham-operated controls. In the liver of adrenalectomized animals 24 hours after adrenalectomy when the rate of de novo purine biosynthesis is increased above control by 70% there was a 200% increase of 5-phosphoribosyl 1-pyrophosphate (PRPP) concentration. The concentrations of purine ribonucleotides showed a 33 and a 24% decrease of ATP and GTP, and 245 and 38% increase of AMP and ADP respectively associated with the unchanged total adenine and guanine nucleotide concentration and a 18% decrease of adenylate energy charge. The specific activity of amidophosphoribosyltransferase (ATase) was not changed. The replacement with corticosterone acetate to adrenalectomized animals for 24 hours partially restored the rate of de novo purine biosynthesis and the concentrations of purine ribonucleotides. These results suggest that the increased rate of de novo purine biosynthesis in adrenalectomized rat liver is compensatory against the increased catabolism of purine ribonucleotides as a result of the increased AMP concentration and that it is mediated by the increased concentration of PRPP. Our study has demonstrated the importance of the physiological amount of adrenocortical hormone to sustain the normal concentrations and the metabolism of purine ribonucleotides in liver.

Adrenalectomy↗

Radical surgery for renal-cell carcinoma: caval neoplastic excision, adrenalectomy, lymphadenectomy, adjacent organ resection.

A radical nephrectomy typically includes early ligation of the renal vessels, excision of the kidney and perinephric tissue, a regional lymphatenectomy, and an adrenalectomy. More controversial may be excision of supradiaphragmatic caval neoplastic extension and adjacent organ resection. Although survival is low in these unfavorable groups of patients, some patients may benefit from the extensive local resection of tumor, including adrenalectomy, lymphatenectomy, caval resection, and resection of adjacent organs.

Adrenalectomy↗

Effect of stress, adrenalectomy and changes in glutathione metabolism on rat kidney metallothionein content: comparison with liver metallothionein.

Eighteen hours of immobilization stress, accompanied by food and water deprivation, increased liver metallothionein (MT) but decreased kidney MT levels. Food and water deprivation alone had a significant effect only on liver MT levels. In contrast, stress and food and water deprivation increased both liver and kidney lipid peroxidation levels, indicating that the relationship between MT and lipid peroxidation levels (an index of free radical production) is unclear. Adrenalectomy increased both liver and kidney MT levels in basal conditions, whereas the administration of corticosterone in the drinking water completely reversed the effect of adrenalectomy, indicating an inhibitory role of glucocorticoids on MT regulation in both tissues. Changes in glutathione (GSH) metabolism produced significant effects on kidney MT levels. Thus, the administration of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased kidney GSH and increased kidney MT content, suggesting that increased cysteine pools because of decreased GSH synthesis might increase kidney MT levels through an undetermined mechanism as it appears to be the case in the liver. However, attempts to increase kidney MT levels by the administration of cysteine or GSH were unsuccessful, in contrast to what is known for the liver. The present results suggest that there are similarities but also substantial differences between liver and kidney MT regulation in these experimental conditions.

Adrenal Glands↗

Effect of adrenalectomy and administration of hypertonic saline on the content of aldehyde fuchsin-positive neurosecretory material and posterior lobe hormones in the median eminence and the neural lobe of rats.

The influence of adrenalectomy and administration of hypertonic saline on the amount of vasopressin, oxytocin, and neurophysin contained in the median eminence and the neural lobe of rats was studied by means of the following methods: (i) morphometric and microphotometric analyses of aldehyde fuchsin-stained histological sections of the neurohypophysis; (ii) immunohistochemical demonstration of vasopressin, oxytocin, and neurophysin in the neurohypophysis, and (iii) radioimmunological measurement of vasopressin and oxytocin in extracts of the median eminence and the neural lobe. Adrenalectomy increases the amount of vasopressin and neurophysin in the external layer of the median eminence but does not change the content of oxytocin. It has no influence on the amount of vasopressin, oxytocin, and neurophysin demonstrable in the inner layer of the median eminence and in the neural lobe two weeks after the operation. Hypertonic saline markedly diminishes the vasopressin, oxytocin, and neurophysin content of the inner layer of the median eminence and the neural lobe but reduces only slightly, if at all, the amount of vasopressin and neurophysin in the outer layer of the median eminence. The findings support the concept that osmotic stress reduces only the vasopressin and oxytocin content of the hypothalamus-neural lobe system and has no or only little influence on the vasopressin content of the outer layer of the median eminence.

Adrenalectomy↗

Influence of maternal adrenalectomy on the ultrastructure of the adrenal gland in neonatal rats.

Maternal adrenalectomy at 7 or 14 days of gestation produced increased cell necrosis within zona reticularis cells on the day of birth and at 24 or 48 h after birth. Small remnants or large portions of adrenocortical cells were present within macrophages. In otherwise normal adrenocortical cells, lipid droplets were incorporated within some mitochondria. Autophagocytosis of single mitochondria was observed within adrenocortical cells. Undoubtedly ultrastructural changes represent stimulation of adrenocortical cells in neonatal rats in response to maternal adrenalectomy.

Adrenal Cortex↗

Scintigraphy of hyperfunctioning adrenal tissue after total adrenalectomy.

The significance of scintigraphic examination in four patients with hyperfunction of adrenal tissue after total adrenalectomy is described. The scintigraphic examination was done 7--8 days after the injection of 1 mCi of 131I-19-iodocholesterol using the Jumbo Thoshiba 202 scintillation camera and Informatek SIMIS 3 data processing system. Noticeable concentration of 131I-19-iodocholesterol occurred in all four patients of, in three cases in the region of the right adrenal gland and in one case in the region of the left one. Scintigraphic examination confirmed the clinical hypothesis that of cushing's syndrome recurred in these patients because of hyperfunctioning adrenal tissue left in the body after the operation. This diagnosis was given confirmed in two cases undergoing repeated operations. The scintigraphic examination allowed accurate localization of the adrenal tissue and facilitated finding it during the next operation. The authors believe that adrenal scintigraphy is at the present time one of the best methods of locating the hyperfunctioning adrenal tissue left in the body during total adrenalectomy.

Adrenal Glands↗

Laparoscopic adrenalectomy. The importance of a flank approach in the lateral decubitus position.

Adrenalectomy is usually performed via transabdominal or posterior approaches. Unfortunately, both approaches are associated with painful postoperative syndromes. Recently, laparoscopic surgery was applied to organ removal. During a period of 12 months, we performed a series of successful laparoscopic adrenalectomies (10 of the right and 11 of the left gland). The pathologies were medullary cyst (1), angiomyolipoma (1), DHEAS hyperplasia (1), primary aldosteronism (2), Cushing's adenoma (3), pheochromocytoma (4), Cushing's syndrome (4), and nonfunctional adenoma (5). A flank approach was taken with four 11-mm trocars. Electrocautery and blunt forceps were used for dissection. The vessels were secured with medium-large titanium clips, and the adrenal was removed in a sterile plastic bag. The average operating time was 2.3 h, and median postoperative stay was 4 days. Two patients required blood transfusion of 2 units postoperatively. We believe this technique is adequate for the surgical removal of adrenal tissue, resulting in less postoperative pain and in rapid recovery. It may also change the surgical management of asymptomatic adrenal lesions.

Adrenal Gland Diseases↗

A quantitative approach to trace the corticotrophs in culture after adrenalectomy.

Anterior pituitaries of adrenalectomized and sham operated adult rats were dispersed by trypsin and cultured for 4 and 8 days. Adrenalectomy caused a moderate increase in number of corticotrophs in both zero-time cell suspensions and cultures. There was a pronounced elevation of immunoreactive ACTH content in both cells and media and an enhanced secretory response to stimulation of cultures with stalk-median eminence extract containing cortiocotropin releasing (CRF) activity. Some cells identified as corticotrophs by a specific immunostaining incorporated tritiated thymidine into their nuclei suggesting their ability to enter the cell cycle. The relatively smaller increase in number of ACTH cells and the considerably higher ACTH producing capacity of the corticotrophs after adrenalectomy seem to be inconsistent with the quantal response model of hormone secretion recently introduced by Rodbard.

Adrenal Glands↗

Studies on the inhibitory effect of indomethacin and meclofenamate on the adrenalectomy-induced increase in plasma renin concentration.

Bilateral adrenalectomy combined with a sodium-deficient diet caused a time-dependent increase in plasma renin concentration in rats. Seventy-two hours after adrenalectomy the inhibitors of prostaglandin biosynthesis indomethacin and meclofenamate diminished the plasma renin concentration by about 50%. This effect was independent of the amount of renin released. Indomethacin and meclofenamate fully retained their ability to reduce the plasma renin concentration when the renal sympathetic nerves or the macular densa cells of the kidneys no longer contributed to renin release. It is concluded that in adrenalectomized rats renal prostaglandins effect the baro-receptor-mechanism in the afferent arterioles and thus enhance renin release.

Adrenalectomy↗

Effects of hypophysectomy, adrenalectomy and (-)-propranolol on ethanol-induced decrease in plasma amino acids.

In previous studies we have demonstrated that an acute dose of ethanol cause an immediate decrease in most plasma amino acids in both man and rat. This effect of ethanol is partly inhibited by the beta-adrenergic antagonist (-)-propranolol, partly by adrenalectomy or hypophysectomy and almost completely by a combination of adrenalectomy with (-)-propranolol. This finding suggests an involvement of both beta-adrenergic mechanisms and steroids from the adrenal cortex in the ethanol-induced decrease in plasma amino acids.

Adrenalectomy↗

Specific activity of Na-K-ATPase after adrenalectomy and hormone replacement along the rabbit nephron.

Both aldosterone and dexamethasone are known to stimulate renal Na-K-ATPase activity although their action is restricted to specific nephron segments: the collecting tubule, the target site for mineralocorticoids, and the thick ascending limb and distal convoluted tubule, the target sites for glucocorticoids. As this stimulation by corticosteroids is very fast, we attempted to establish whether it occurs through de novo synthesis of new Na-K-ATPase units or by increasing the specific activity of the Na-K-ATPase units already present. For this purpose we studied the effects of aldosterone and dexamethasone on Na-K-ATPase specific activity in microdissected nephron segments from adrenalectomized rabbits. This specific activity was determined by the ratio of ATPase activity over the apparent number of catalytic units, as measured by specific 3H ouabain binding. In the proximal tubule, neither adrenalectomy nor steroid replacement altered Na-K-ATPase activity or the apparent number of catalytic sites. In other nephron segments, adrenalectomy reduced Na-K-ATPase activity and specific 3H ouabain binding concomitantly, and therefore left this enzyme's specific activity unaltered. In the cortical and outer medullary collecting tubules, 10 micrograms/kg aldosterone simultaneously restored both the activity and apparent number of catalytic units of Na-K-ATPase to their control levels, and therefore did not modify the specific activity of the pump. Conversely, 100 micrograms/kg dexamethasone increased Na-K-ATPase activity in the thick ascending limb and distal convoluted tubule without changing the apparent number of catalytic units.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Glucose uptake and triglyceride synthesis in adipose tissue of spontaneously and renal hypertensive rats (alterations revealed by adrenalectomy).

Rats with renal and spontaneous hypertension do no differ from control normotensive rats in 14C-glucose uptake and triglyceride synthesis by the adipose tissue in vitro, both with and without insulin stimulation. Adrenalectomy (which eliminates the stabilizing effect of the corticosteroid hormones on the adipocyte membrane) reveals the differences between the hypertensive and normotensive rats in the response of the adipose tissue to insulin. While the adrenalectomized control rats show a significantly lowered "sensitivity" of the adipocytes to insulin, the adrenalectomized hypertensive rats do not reveal a noticeable change in glucose uptake and triglyceride synthesis under insulin stimulation of glucose transport (the adipose tissue of hypertensive rats "doesn't notice" adrenalectomy). The data obtained may indicate changes in the properties of the adipocyte membranes of rats with chronic arterial hypertension and suggest the presence of an extensive alteration of the function of cell membranes in both types of hypertension.

Adipose Tissue↗