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Alpha- and beta-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy.

In many tissues adrenergic responsiveness may be impaired by chronic exposure to adrenergic agonists. We examined the effects of high levels of circulating norepinephrine and epinephrine to alpha 2- and beta 2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of beta 2-receptors prior to removal of the tumour was diminished by 67% (500 +/- 160 sites/cell, n = 7 vs 1500 +/- 350 sites/cell, n = 29; P less than 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 +/- 0.16 nmol/l in phaeochromocytoma, 0.52 +/- 0.19 nmol/l in controls) were not significantly different in MNL preparations from the two groups. MNL adenylate cyclase activities in response to 10 mumol/l (-) isoproterenol was lower in the patients (7.5 vs 22 pmol cAMP/10(6) MNL/10 min; P less than 0.001). Conversely, the number of alpha 2-adrenoceptors on platelets and the affinity of these receptors for [3H]yohimbine did not differ between patients and controls. Ensuing adrenalectomy the regeneration of the beta-adrenergic cAMP-system results from a two-phase process. A prompt but moderate restoration was followed by a gradual rise to the normal range within about 1 to 2 months indicating the dynamic character of the beta 2-adrenoceptor cAMP-system in MNL. We conclude that the downregulation observed in MNL, which appears not to be operative in human platelets, represents only one mechanism of feedback control in the sympatho-adrenal-system protecting tissues from prolonged stimulation by excessive catecholamines.

Adrenal Gland Neoplasms↗

Enhanced anterior pituitary mitotic response to adrenalectomy after multiple glucocorticoid exposures.

OBJECTIVES: Glucocorticoid withdrawal in man is associated with transient but sometimes prolonged impairment of hypothalamo-pituitary-adrenal axis secretory responsiveness. This has led to continued concern in the clinical arena. The acute anterior pituitary response to glucocorticoids in the rat includes apoptosis-mediated deletion of a cell population. Whilst continued cell turnover following glucocorticoid withdrawal and the potential for differentiation of uncommitted precursor cells and transdifferentiation of other secretory cell types predicts that, given sufficient time, complete anterior pituitary trophic recovery is likely, this hypothesis has not previously been tested. DESIGN AND METHODS: We have quantified pituitary mitotic and apoptotic rate, as well as corticotroph number and pro-opiomelanocortin transcript prevalence, together with hypothalamic corticotrophin-releasing hormone and vasopressin transcript prevalence 5 weeks after three short dexamethasone treatments each separated by a week. Bilateral adrenalectomy was then carried out as a maximal secretory and trophic stimulus, and the response to a fourth dexamethasone treatment assessed 1 week later. RESULTS: Anterior pituitary mitotic index was significantly higher in rats previously exposed to dexamethasone compared with age-matched controls exposed to dexamethasone for the first time. No differences were found in the subsequent apoptotic response to a fourth dexamethasone treatment or in the levels of paraventricular corticotrophin-releasing hormone or vasopressin transcripts or pituitary pro-opiomelanocortin transcripts. CONCLUSIONS: These data indicate that full recovery of pituitary mitotic activity takes longer than the recovery of secretory parameters, and suggest that, for several weeks after glucocorticoid exposure, the ability of the pituitary to meet fresh demands placed on it may be suboptimal.

Adrenalectomy↗

Differential effects of adrenalectomy on the prolactin-induced suppression of LH and FSH secretion after castration in male rats.

Hyperprolactinaemia inhibits gonadotrophin secretion in males and females of many species. The aim of this study was to determine the role of the adrenal gland in mediating the inhibitory effects of prolactin by contrasting the effects of acute hyperprolactinaemia on LH and FSH secretion in adrenal-intact and adrenalectomized rats with and without physiological corticosterone replacement. Adult male rats were administered purified ovine prolactin every 12 h (2.4 mg per injection s.c.) beginning at the time of castration. Blood samples were collected every 3 h for 36 h, then every 12 h until 10 days after castration. Ovine prolactin significantly reduced LH secretion in all groups from approximately 15 to 48 h after castration. In contrast, plasma FSH concentrations were reduced by ovine prolactin from 21 to 48 h only in the adrenal-intact rats and not in the adrenalectomized or adrenalectomized plus corticosterone groups. In all groups, ovine prolactin inhibited endogenous prolactin secretion in rats by short-loop autofeedback as soon as 3 h after the first ovine prolactin injection and throughout the 10 days of the study. Adrenalectomy per se, with or without corticosterone replacement, also had a differential effect on LH and FSH secretion after castration, causing only a transient delay in the rise in LH after castration, but inducing a significant and long-lasting inhibition of FSH secretion. The results demonstrate that ovine prolactin-induced suppression of LH secretion after castration occurs with or without the adrenal glands. Suppression of FSH secretion after castration by ovine prolactin, however, may involve an adrenal component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Influence of unilateral adrenalectomy on renin-angiotensin-aldosterone system in primary aldosteronism.

In a study of 14 patients (11 Japanese and 3 white North Americans) with aldosterone-producing tumor carried out within 2 to 4 weeks after unilateral adrenalectomy, both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) increased almost normally with short-term sodium depletion and upright posture. Aldosterone excretion rate (AER) also increased significantly with sodium depletion, and was normally suppressed by sodium loading. Highly significant correlations were observed between PRA and PAC (r=0.89, p < 0.001) or AER (r=0.88, p < 0.001) ater operation, whereas there had been no such correlation before operation. Either physiological or laboratory findings were normalized or markedly improved in all cases although pathohistological diagnosis was made as adenomatous hyperplasia in 10 out of 11. These results indicate that within 4 weeks of operation PRA and the remaining adrenal gland can almost normally respond to stimuli such as sodium depletion and upright posture regardless of the amount of spironolactone given preoperatively.

Adrenal Gland Neoplasms↗

The effects of adrenalectomy on the harderian gland of the Wistar albino rats.

Harderian glands of the Wistar albino rats normal and adrenalectomized were investigated by light microscopy. In normal, these glands have a tubuloalveolar structure. The gland is located in the medio posterior aspect of the orbit. It is lobulated and appears homogeneous in colour and texture. Harderian gland consist of tubules with wide lumina lined by a single layer of columnar epithelial cells surrounded by myoepithelial cells within their basal lamina. It contains porphyrin pigment which is stored as solid intraluminal deposits. The glandular epithelium possesses two cell types, termed A and B. Type A cells are more numerous. The single excretory duct of the gland is directly continuous with endpieces at the hilus and opens nasally and ventrally to the third eyelid. The excretory duct is accompanied by many acini of small serous glands around it. The tubuloalveoli of the gland is not divided into lobules. There is no branched duct system within the gland. The secretion seems to be associated with porphyrins, is essentially released by exocytosis, but holocrine secretion also occurs. The single excretory duct is lined by a stratified epithelium. The gland is surrounded by a collagenous capsule. The adrenalectomy, caused degenerative changes in the glands. Epithelial height was lower than in normal gland epithelium. Most of the acini were completely disorganised. The acinar lumina were filled with porphyrin debris. The results suggest that rat harderian glands are sensitive to adrenal androgen changes in both male and female rats.

Adrenalectomy↗

[Octreotide + bilateral adrenalectomy in the management of ACTH-producing carcinoid tumors].

Cushing's syndrome (CS) due to ectopic ACTH secretion has a high morbidity and mortality. Thus, rapid treatment of ectopic CS is mandatory. Carcinoid tumors associated with ectopic ACTH (CTu-ACTH) syndrome represent a more severe clinical picture, due to the carcinoid symptoms that worsen the hypercortisolism state. Management of patients with CTu-ACTH should include the control of hypercortisolism, as well as the carcinoid disturbance. We report 3 patients (2F, 1M) with CTu-ACTH (2 pancreatic, 1 occult) who presented with clinical manifestations of CS (n= 3) and carcinoid syndrome (2): 2 were initially investigated for CS and 1 carcinoid syndrome. In all hypokalemia, hypertension and diabetes mellitus were associated with severe hypercortisolism and high ACTH levels. Administration of octreotide-LAR reduced ACTH levels from 230,000 to 30,000 pg/ml in patient 1, and controlled symptoms of carcinoid syndrome and neoplasic lesions in patient 2; treatment with subcutaneous octreotide in patient 3 controlled carcinoid syndrome and partially reduced symptoms of hypercortisolism. All 3 patients were submitted to bilateral adrenalectomy to control CS. Our data show that combined anti-neoplastic therapy may contribute to the stabilization and/or definitive control of CTu-ACTH.

Adrenalectomy↗

Effects of adrenalectomy and adrenal enucleation on liquid gastric emptying in rats.

The effects of adrenalectomy and adrenal enucleation on liquid gastric emptying were studied in male Wistar rats that were adrenalectomized, adrenal enucleated (AE) or sham operated (SH). The animals in the first group had free access to a 1% NaCl solution (ADS), while the animals in the second and third groups were divided into two subgroups, which ingested either tap water (AEW, SHW) or 1% NaCl solution (AES, SHS). The gastric emptying study was performed on the 16th post-operative day. Three test meals labeled with phenol red (6 mg/dl) were used (0.9% NaCl, 1.8% NaCl and 5% glucose). Percent gastric retention was determined 10 min after orogastric infusion of the NaCl test meals and 15 min after the glucose meal. Gastric retention of the ADS subgroup was significantly lower (P<0. 01) (median = 19.8% vs 25.5% for SHW, vs 31.9% for SHS, vs 25.7% for AEW, and vs 27.1% for AES) for the 0.9% NaCl test meal and for the 1. 8% NaCl test meal (33.5% for ADS vs 47.5% for AEW and 50.6% for AES). When 5% glucose was used as a test meal, gastric retention was similar for all subgroups. These results suggest that ablation of the adrenal cortex results in increased gastric emptying of an isosmolar NaCl meal.

Adrenal Medulla↗

Effects of adrenalectomy on the release of follicle-stimulating hormone and the onset of puberty in female rats.

The involvement of the adrenal gland in the release of gonadotrophins and the onset of puberty in female rats was studied. Two and four days after adrenalectomy (ADX) on either day 5 or 10 after birth, a significant decrease in the concentration of FSH was found; 4 days after ADX on either day 15 or 20, FSH concentrations had increased significantly compared with sham-operated and/or intact controls. However, in the rats adrenalectomized on day 15 or 20, the body weights were lower than in control rats. Relative uterine weights (mg/100 g body wt) in adrenalectomized rats never differed from those of control rats. A delay in the time at which vaginal opening and the first oestrus occurred was found in rats adrenalectomized at 20 or 25 days of age; however this delay was accompanied in these rats by a retardation in the gain in body weight. It is argued that the effects of ADX on both the release of gonadotrophins and the onset of puberty are primarily, and presumably exclusively, due to the effects on general bodily development (expressed in body weight). The lack of effect of ADX on uterine weight supports the hypothesis that 'oestrogen-like' products from the adrenal gland are not biologically active as oestrogens.

Adrenal Glands↗

Effects of neonatal adrenalectomy and castration on hormonal changes in pubertal bulls.

Plasma samples from intact, adrenalectomized, adrenalectomized and castrated and castrated bulls were assayed for LH, testosterone, androstenedione and oestradiol-17 beta from birth to 26 weeks of age. The adrenalectomized bulls, unlike the intact bulls, failed to show a rise in androstenedione at 14.5 weeks of age or a rise in testosterone at 20 weeks of age. Testosterone levels in the castrated animals remained below 0.4 ng/ml whereas androstenedione reached levels similar to those in intact bulls by 26 weeks of age. In all animals the concentration of oestradiol-17 beta in plasma remained below 25 pg/ml, although intact bulls had the highest levels. Levels of LH rose after castration but not after adrenalectomy. These data show that in bull calves absence of the adrenal glands during prepuberty delays the rise in pubertal testosterone by at least 10 weeks.

Adrenalectomy↗

Effects of handling, anaesthesia, ovariectomy and adrenalectomy on serial measurements of plasma progesterone in 16-day pregnant rats.

The basal concentrations of progesterone in plasma of 16-day pregnant rats were measured after seven different sampling procedures. Progesterone concentrations in serial samples from rats held at the time of sampling (restrained group) were compared with those obtained from rats allowed to remain free in their cage (free group). In addition, the effects on plasma progesterone concentrations of anaesthesia induced by ether or pentobarbitone sodium, and of adrenalectomy and/or ovariectomy were studied. Over the 8-h sampling period, progesterone concentrations in the plasma of restrained rats, with or without anaesthesia, were about 30% higher and more variable than those in free rats. Progesterone concentrations rose sharply over the first 30 min in restrained rats and in those treated with ether. Rats adrenalectomized the day before sampling did not show this early rise and their progesterone concentrations were similar to those of free rats. Progesterone concentrations were lowest in ovariectomized rats which had also been adrenalectomized. These findings show that adrenal secretion can increase plasma concentrations of progesterone in pregnant rats which have been handled or anaesthetized. Such a rise might well modulate the effects of experimental stimuli.

Adrenalectomy↗

Effect of adrenalectomy on LH release in sheep during the anoestrous season.

An experiment was conducted to measure LH pulse frequencies in bilaterally adrenalectomized Ile-de-France ewes during the mid-anoestrous season. Seven ewes were adrenalectomized under general anaesthesia and maintained on daily injections of 3 mg deoxycorticosterone acetate (DOCA). Adrenalectomy did not affect the patterns of LH release and the mean intervals between pulses in the adrenalectomized and sham-operated control ewes were 48 and 52 min respectively. Small implants of oestradiol significantly reduced the frequency of LH pulses in both groups and, in the presence of oestradiol, there were no differences in LH release between adrenalectomized and sham-operated ewes, with the mean interpulse intervals being 91 and 89 min respectively. In a second experiment, designed to assess the effects of DOCA on LH release, the mean interpulse intervals in unoperated control ewes (46 min) and unoperated ewes given daily injections of 3 mg DOCA (47 min) were similar to those observed in adrenalectomized and sham-operated ewes. In the presence of small implants of oestradiol, the combination of DOCA and oestradiol decreased the pulse frequency significantly more than oestradiol alone (mean interpulse intervals of 85 and 65 min respectively) suggesting that DOCA may act as a progestagen in sheep. Thus alternative treatments to DOCA for the maintenance of adrenalectomized sheep must be found for future studies on the role of adrenal steroids in the reproductive system. It appears that adrenal steroids do not play a major role in the seasonal changes in LH release in the ewe.

Adrenal Glands↗

Glucose tolerance and insulin secretion after adrenalectomy in mice made obese with gold thioglucose.

The effect of adrenalectomy (ADX) on glucose tolerance and insulin secretion was examined in conscious mice made obese by a single injection of gold thioglucose (GTG). To facilitate such a study a chronic jugular catheter was implanted into the mice at the time of performing the ADX or sham-ADX. One week after ADX, the body weight (GTG-obese+sham-ADX, 35.6 +/- 0.6 g; GTG-obese+ADX, 33.1 +/- 0.6 g; P < 0.05) and glycogen content of the liver (GTG-obese+sham-ADX, 2.4 +/- 0.2 mumol/liver; GTG-obese+ADX, 1.6 +/- 0.1 mumol/liver; P < 0.05) of GTG-injected mice were reduced. Plasma glucose concentrations, in both the overnight fasted state and in response to an intravenous glucose load were also reduced following ADX of GTG-obese mice, but not to the level of the sham-ADX control mice. However, ADX completely normalized plasma insulin concentrations in both the basal state and also in response to a glucose load, as indicated by the finding that the integrated insulin secretory response of the ADX GTG-obese mice was not different from that of sham-ADX control mice (control+sham-ADX, 192 +/- 5 min.microU/ml; GTG-obese+ADX, 196 +/- 10 min.microU/ml). The effects of ADX on carbohydrate metabolism were not restricted to GTG-injected mice, as ADX of control mice decreased fasting plasma glucose levels and reduced liver glycogen and plasma insulin concentrations. The normalization of insulin release in ADX GTG-obese mice occurred while these mice were still obese and glucose intolerant. This suggests that the decreased insulin release was not due solely to an ADX-induced improvement in insulin sensitivity and/or weight loss. Removal of central glucocorticoid effects on the parasympathetic stimulation of insulin release may play a role in the reduced insulin release observed after ADX of obese and control mice, although peripheral effects of glucocorticoid deficiency on glycogen synthesis in the liver may also influence whole animal glucose homeostasis.

Adrenalectomy↗

Adrenalectomy alters the sensitivity of the central nervous system melanocortin system.

Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Thus, glucocorticoids appear to play a key role to promote positive energy balance in normal and pathological conditions. By comparison, central nervous system melanocortin signaling provides critical inhibitory tone to regulate energy balance. The present experiments sought to test whether glucocorticoids influence energy balance by altering the sensitivity to melanocortin receptor ligands. Because melanocortin-producing neurons are hypothesized to be downstream of leptin in a key weight-reducing circuit, we tested rats for their sensitivity to leptin and confirmed reports that the hypophagic response to third ventricular (i3vt) leptin is increased in ADX rats and is normalized by glucocorticoid replacement. Next we tested rats for their sensitivity to the melanocortin agonist melanotan II and found that, as for leptin, ADX enhanced the hypophagic response via a glucocorticoid-dependent mechanism. The central nervous system melanocortin system is unique in that it includes the endogenous melanocortin receptor antagonist, AgRP. The orexigenic effect of i3vt AgRP was absent in ADX rats and restored by glucocorticoid replacement. We conclude that the potent weight-reducing effects of ADX likely involve heightened responsiveness to melanocortin receptor stimulation.

Adrenalectomy↗

Hyperadrenocorticism treated with metyrapone followed by bilateral adrenalectomy in a cat.

A 6-year-old spayed female cat was evaluated for uncontrolled diabetes mellitus and poor hair coat. Clinicopathologic abnormalities included high serum activity of liver enzymes, hyperglycemia, hypercholesterolemia, glucosuria, and an exaggerated response to ACTH stimulation. Abdominal ultrasonography revealed large adrenal glands. Hyperadrenocorticism was diagnosed. Treatment for a facial abscess was instituted along with administration of metyrapone for hyperadrenocorticism. After stabilization, bilateral adrenalectomy was performed. The cat recovered without complications and has remained clinically normal for 5 months with treatment of desoxycorticosterone pivalate and prednisone. Treatment with metyrapone appeared to stabilize the cat metabolically and clinically prior to surgery.

Adrenalectomy↗

Serum luteinizing hormone in prepuberal gilts after ovariectomy or adrenalectomy.

Serum luteinizing hormone (LH) concentrations after ovariectomy (OVX) and adrenalectomy (ADX) were studied in the prepuberal gilt. In Exp.I, gilts, 170 to 175 d of age and 80 to 85 kg body weight, were OVX (n = 5) or sham-OVX (n = 5). Blood samples were collected via jugular vein cannulae every 30 min for 8 h on d 1, 3, 5, 7 and 21 after surgery. In Exp. II, blood samples were collected via jugular vein cannulae every 30 min for 12 h on d 3, 5, 7 and 14 after surgery from five ADX, five sham-ADX and five nonsurgical control gilts of similar ages and weights as in Exp. I. In Exp. I, basal serum LH concentrations (means +/- SE, ng/ml) over all days were greater (P less than .05) in OVX (2.9 +/- .1) than in sham-OVX (1.1 +/- .2) gilts. Average basal serum LH concentrations were greater (P less than .05) on d 1 for both treatments than all other days sampled. The frequency of LH peaks (means +/- SE/8 h) was also greater (P less than .01) for OVX (3.5 +/- .3) than sham-OVX gilts (1.7 +/- .2). Similarly, the mean concentration of the LH peaks was greater (P less than .01) for OVX (4.1 +/- .2 ng/ml) than sham-OVX gilts (2.1 +/- .2 ng/ml). In Exp. II, mean basal serum LH concentrations, frequency of LH peaks and mean concentration of the LH peaks were similar for all treatments on each day sampled. The frequency of LH peaks (means +/- SE/12 h) was greater (P less than .05) on d 3 (3.4 +/- .3) than on d 5 (2.3 +/- .3) and d 7 (2.1 +/- .4), but similar to d 14 (2.8 +/- .5) in all treatments. In prepuberal gilts, ADX failed to influence serum LH concentration, whereas OVX caused a significant increase in serum LH concentration. We suggest that the ovary is the major steroid-secreting gland having a negative feedback on pituitary gonadotropin production in the prepuberal gilt.

Adrenal Glands↗

Effects of adrenalectomy and glucocorticoids on puberty in gilts reared in confinement.

The effect of adrenal function and flumethasone (FM, a synthetic glucocorticoid) on induction of puberty in crossbred gilts raised in confinement was examined in two experiments. In Exp. 1, gilts were adrenalectomized (Adx) or subjected to sham adrenalectomy (Sham) between 140 and 160 d of age. Twenty days later indwelling jugular catheters were implanted in Adx, Sham and another group of intact gilts designated as Controls, and the gilts were moved from confinement to outdoor pens and checked daily for estrus with a mature boar. Fewer (P less than .05) Adx (1/11) than Sham (9/14) gilts showed estrus and ovulated by 205 d of age. Response of Control gilts (6/14) was not different from the other groups. Although Adx gilts received 40 mg cortisone acetate and 10 mg deoxycorticosterone acetate daily throughout the experiment, mean plasma glucocorticoids were lower (P less than .05) in Adx (24 +/- 4.7 ng/ml) than in either Sham (47 +/- 8.1 ng/ml) or Control (44 +/- 6.1 ng/ml) gilts. Experiment 2 was conducted to determine whether FM given to Adx gilts immediately after surgery could have inhibited estrus and ovulation. Intact gilts received a total of 27.5 (FM1) or 17.5 (FM2) mg FM over 4 d between 150 and 160 d of age before relocation and boar exposure 20 d later. Control gilts received no injections. Nine of 13 FM-treated but none of the Control gilts showed estrus. It is concluded from these results that the adrenal glands may facilitate the onset of puberty in gilts through increases in glucocorticoid production, but that this is not required for puberty to occur.

Adrenalectomy↗

Effects of maternal bilateral adrenalectomy on fetal rat cerebral cortex.

We investigated the effects of maternal bilateral adrenalectomy (ADX) on fetal rat cerebral cortices by assessing morphological and morphometrical parameters in light and electron microscopy studies. Pregnant adult rats underwent ADX on day 4 of gestation. Embryonic brain tissue from control and ADX groups were examined at each of the 10 embryonic stages, days 11 through 20 (E11-E20). Control and adrenalectomized pregnant females were sacrificed at each fetal stage, fetuses were removed from the uterine horns, and their brain tissue was processed for light and electron microscopy examination. In the ADX fetuses, the cortical laminae were thicker and overall cortex thickness was greater, but structural differentiation in the primitive cortical layers was delayed compared with that observed in controls. Apart from the differences in embryonic cell development noted at the structural level, we found no noticeable ultrastructural differences between the cerebral cortices of ADX and control fetuses at any of the stages studied. Overall, the ADX group's cortical tissue exhibited a greater degree of cell migration, an extended proliferative period in the cortical layers with the highest proportion of mitotic activity, and a greater thickness than that of control specimens. We believe that by eliminating the inhibitor effects of glucocorticoids, ADX effectively induces mitotic activity and extends the proliferative periods in developing cerebral cortex.

Adrenal Glands↗

Left-sided laparoscopic adrenalectomy.

Laparoscopic transperitoneal adrenalectomy was performed in a 42-year-old female with a left adrenocortical adenoma causing Conn's syndrome. No technical problems occurred during surgery and the patient recovered quickly.

Adrenal Cortex Neoplasms↗