Adrenalectomy-induced granule cell death is predicated on the disappearance of glucocorticoid receptor immunoreactivity in the rat hippocampal granule cell layer

In this study, we observed the changes of glucocorticoid receptor (GR)-immunoreactivity (ir) and cell death in the rat hippocampal granule cell layer at various periods after adrenalectomy (ADX). Our results revealed that all of the rats shortly after ADX showed a rapid loss of GR-ir and subsequent appearance of degenerating cells in the granule cell layer. One month after ADX, however, about 80% of the rats displayed a restoration of GR-ir and the absence of degenerating cells in the granule cell layer, and this phenomenon was successively noted for 6 months. Hippocampal structural destruction 3 and 6 months after ADX was found in about 20% of the rats with loss of GR-ir in the granule cell layer; the ADX rats with even weak GR-ir in this area had a normal hippocampus. The treatment of rats with synthetic GR agonist, dexamethasone, immediately after ADX prevented the loss of GR-ir and significantly reduced the number of degenerating cells in the granule cell layer. Our results clarified that granule cell death after ADX was necessarily accompanied by the disappearance of GR-ir in the granule cell layer, suggesting that ADX-induced granule cell death is predicated on the loss of GR-ir and that the presence of GR-ir in this area may be important for granule cell survival.     

Surgical Treatment of Adrenal Metastasis Following hepatectomy for Hepatocellular Carcinoma

In three patients who underwent hepatectomy for solitary hepatocellularcarcinoma (HCC), adrenal metastases, on the right sides of twopatients and the left side of the third were subsequently detectedby ultrasonography (US) and/or computed tomography (CT), andsuccessfully resected after an average interval of 16 monthsfrom hepatectomy. There were no metastatic lesions in the lung,lymph node or bone. Two patients, however, who were found tohave metastasis in the right adrenal also had multiple smallrecurrent foci in the residual liver. The latter were controlledby arterial embolization therapy and the patients are aliveat 12 and three months post-adrenalectomy. In the other patient,with left adrenal metastasis, the serum alpha fetoprotein levelof 3,000 ng/ml returned to normal and he is doing well threeand a half years after adrenalectomy. Since there is no effectivetherapy for metastatic adrenal HCC after hepatectomy, surgerywould appear to be indicated, should no other distant metastasisbe recognized clinically.     

Proximal tubular reabsorption of inorganic phosphate in adrenalectomized rats

Micropuncture studies have been performed in adrenalectomized (Adr.X) and sham-adrenalectomized (Sham-Adr.X) rats in order to examine the effects of acute adrenalectomy on the inorganic phosphate (Pi) transport in the convoluted proximal tubule of superficial nephrons under free flow conditions. Adrenalectomy diminished single nephron glomerular filtration rate from 27.0±12.4 (Sham-Adr.X) to 10.9±7.1 nl/min (mean ± S.D.,P<0.001), increased the inulin ratio (tubular fluid-to-plasma) at the end of the proximal convolution from 2.14±0.60 (Sham-Adr.X) to 3.62±1.67 (P<0.001) and decreased both the (TF/P)_Pi ratio from 0.87±0.20 (Sham-Adr.X) to 0.46±0.28 (P<0.001) and the fractional delivery of inorganic phosphate into the loop of Henle from 44±18 (Sham-Adr.X) to 15±10% (P<0.001). Thus the fractional reabsorption of inorganic phosphate in the convoluted proximal tubule in acutely Adr.X rats was higher than in Sham-Adr.X animals. It is concluded that glucocorticoid hormones play an important role in the regulation of the fractional reabsorption of Pi in the proximal tubule. The mechanism of this regulation is discussed.Supported by the Deutsche Forschungsgemeinschaft (Fr239/7). Parts of this work [6] have been presented at the 52th Meeting of the German Society of Physiology, Kiel. FRG, 1979, and at the XIIIth Symposion of the German Society of Nephrology, Berlin, 1979     

Electrogénèse cardiaque du rat surrénalectomisé, interprétation en fonction des variations de gradients ioniques et de perméabilités membranaires

Summary The adrenalectomy induces a 15–20 mV decrease in cardiac resting membrane potential; acute disturbances of ventricular action potential recorded with ultramicroelectrode technique are also observed.These electrical changes can be reported to variations of ionic concentrations in adrenalectomized rats. The calculated values of equilibrium potentials for K⁺, Na⁺ and Cl^– could explain the decline in resting potential, but some experiments show that modifications of the membrane permeabilities could be also involved in the depolarizing processes.The disturbances of action potential result from the low resting potential.This fundamental study might contribute to a better interpretation of heart failure in adrenal insufficiency.

Je remercie vivement M. le Professeur Gargouïl de ses conseils éclairés qui ont permis de mener à bien ce travail.     

A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats

Rationale Acute 1-day food deprivation reinstates heroin seeking in rats via a leptin-dependent mechanism. However, leptin has no effect on footshock- or heroin-priming-induced reinstatement of drug seeking. These data may indicate that the neuronal systems underlying food-deprivation-induced reinstatement are dissociable from those involved in reinstatement induced by footshock stress.Objectives We used the reinstatement procedure to examine the roles of the adrenal stress hormone, corticosterone, and brain corticotropin-releasing factor (CRF) in acute food-deprivation-induced reinstatement of extinguished heroin seeking in rats.Materials and methods The rats were trained to press a lever for heroin (0.05−0.1 mg/kg/infusion, i.v.) for 10 days. Experiment 1: After heroin self-administration training, the rats were divided into two groups, which received either bilateral adrenalectomy surgery or sham surgery. Next, the rats were given 7–10 days of extinction training (during which lever presses were not reinforced with heroin). The rats were subsequently tested for reinstatement after acute (21 h) food deprivation. Experiment 2: After heroin self-administration and extinction training, the rats were tested for reinstatement induced by acute food deprivation. Before the test session, the rats were given intracerebroventricular injections of the CRF receptor antagonist α-helical CRF (0, 3, or 10 μg/rat).Results Adrenalectomy had no effect on the extinction behavior or acute food-deprivation-induced reinstatement of heroin seeking. The CRF receptor antagonist, α-helical CRF, dose-dependently blocked food-deprivation-induced reinstatement.Conclusions The present data suggest that, as demonstrated for footshock-induced reinstatement of drug seeking, brain CRF, but not corticosterone, plays a critical role in acute food-deprivation-induced reinstatement of heroin seeking.     

Pharmacological modification of shock potentiated amphetamine lethality

The ability of the acute application of inescapable footshock to potentiate d- and d,l-amphetamine in rodents has previously been ascertained. The present study confirmed these results and demonstrated a similar interaction with l-amphetamine. Aggregation further enhanced this potentiation. Prior subacute exposure to shock did not prevent the potentiated lethality. Shock potentiated amphetamine lethality was antagonized by pretreatment with agents which indirectly reduce catecholamine release (6-hydroxydopamine, α-methyl-p-tyrosine) and by bilateral adrenalectomy. However antagonism did not result from pretreatment with the adrenergic blocking agents propanolol and phenoxybenzamine. Pretreatment with methoxamine and hydrocortisone likewise did not afford protection. However pretreatment with haloperidol and pentobarbital completely antagonized the potentiated lethality whereas morphine and fenfluramine pretreatment did not provide protection. Shock potentiated amphetamine lethality was enhanced by pretreatment with physostigmine and neostigmine but was antagonized by pretreatment with methylatropine. However atropine pretreatment enhanced lethality. It would appear that the release of norepinephrine from the brain and/or the adrenal medulla either is directly involved in mediating amphetamine lethality or in mediating the effects of acute stress on emphetamine's lethal actions.     

Effect of prolonged exercise on the level of triglycerides in the rat liver

Summary This study examined the effect of prolonged exercise on the level of triglycerides (TG) in rat liver. The rats were divided into groups: 1-control, 2-treated with nicotinic acid, 3-fed with glucose during exercise, 4-fasted, 5-adrenalectomized, 6-adrenalectomized and fed with oil. In the control group, there was gradual accumulation of TG in the liver and their level was doubled at exhaustion as compared to the resting value. Nicotinic acid lowered the resting level of TG and prevented their accumulation during exercise. Administration of glucose during exercise partially prevented the increase in TG level in the liver. In rats fasted for 24 h before exercise, the net increase in liver TG level during exercise was similar to that in the controls. Adrenalectomy, like nicotinic acid, lowered TG level at rest and prevented its increase during exercise. Feeding the adrenalectomized rats with oil elevated the plasma free fatty acid level but did not result in accumulation of TG in the liver, either at rest or during exercise. It is concluded that prolonged exercise results in accumulation of TG in the liver and that the process depends on the supply of free fatty acids and glucose and requires the presence of glucocorticoids.This work was supported by the Polish Central Programme for Basic Research 06-02.     

Evidence of central influences on blood glucose level: malathion hyperglycemia.

To suppress the hyperglycemic effect of malathion in rats, a smaller amount of atropine was required when the drug was injected by intraventricular (i. vent.) than s.c. Pentobarbital, but not diazepam, blocked the hyperglycemic response. The results suggest that central accumulation of acetylcholine was the mediator of the response. Since hyperglycemia was not abolished by adrenalectomy and/or hypophysectomy, a hypothesis is presented to explain how central accumulation of acetylcholine might cause hyperglycemia.     

Bilateral pheochromocytoma during pregnancy

Background Pheochromocytoma is a rare disease of the chromaffin cells that secrete catecholamines. It may occur during pregnancy. Bilateral pheochromocytoma in pregnancy is even rarer.Case A 26-year-old woman, gravida 2, para 0-0-1-0, 18 weeks pregnancy, was initially seen with elevated blood pressure (170/100 mmHg) and mild headache. The cause of hypertension was conventionally investigated and bilateral pheochromocytoma was finally searched for and found. Bilateral adrenalectomy was undertaken at 23 weeks gestation and Cesarean section was performed at 31 weeks gestation due to intrauterine growth retardation (IUGR) and compromised fetal well-being. The maternal outcome was uneventful and the baby was physiologically complicated only by neonatal jaundice.Conclusion Pheochromocytoma should be searched for in the conventionally differential diagnosis in hypertension during pregnancy, especially in the young. Early diagnosis and proper management with medical treatment followed by surgical removal of the tumor usually result in good maternal and fetal outcomes.     

Nutritional influences on dietary selection patterns of obese and lean Zucker rats

Little is known about the behavioral, nutritional, and metabolic events that control dietary intake quality. Two experiments are described that manipulate nutritional conditions that have been hypothesized to affect dietary item choice so as to assess what effect, if any, the added factor of genetic obesity has in modifying the response to these manipulations. In the first experiment, 5 week old male obese and lean Zucker rats were fed a diet that varied in protein content (10%, 20%, or 60% casein by weight) for ten weeks. They were then allowed to select a diet from three separate macronutrient sources (casein, starch, or corn oil). Although body weights at the end of the 10 week maintenance period were markedly different, selection patterns were not influenced by pre-feeding different levels of protein. Obese rats selected a diet that was higher in fat and lower in protein than the diets composed by lean rats. In the second experiment, four groups of 7 month old obese and lean Zucker rats were given access to one of four diets that varied in protein content (5%, 10%, 15%, or 20% casein by weight). In addition, each rat was periodically given access to a 32% sucrose solution. Access to sucrose promoted increases in total caloric intake, independent of the protein content of the diet. Obese rats typically ate more calories per day than did their lean littermates. Results from these experiments suggest that food item selection is determined more by factors associated with obesity than by factors associated with dietary history.