Endocrinologia experimentalis最新文献

A site of action of adrenergic drugs and type of receptors involved in stimulating the pituitary-adrenocortical activity, assessed indirectly through corticosterone (CS) secretion, was investigated in conscious rats. Adrenergic drugs were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), the antagonists always 15 min prior to the agonist and 1 h later the trunk blood was collected for CS determination. Phenylephrine (PHE) (alpha 1-agonist) given by either route increased dose-dependently the serum CS levels. Such effect of PHE given i.p. was abolished by i.p. pretreatment with prazosin (PRA) (alpha 1-antagonist), and similar effect of i.c.v. administered PHE was considerably suppressed by i.c.v. pretreatment with PRA. I.c.v. pretreatment with yohimbine (YO) (alpha 2-antagonist), did not influence the effect of PHE. Clonidine (CLON) given i.c.v. significantly increased the serum CS level and such effect was halved by i.c.v. pretreatment with either YO and PRA. I.p. administered PRA did not decrease the CLON-induced CS response. YO given i.p. considerably reduced the CLON-induced CS response in both low and high doses thus indicating the interaction with pre- and post-synaptic alpha-adrenoceptors. These results suggest that PHE activated the pituitary-adrenocortical axis by a selective stimulation of alpha 1-adrenoceptors located in the hypothalamus and possibly on anterior pituitary corticotrophs. CLON seems to stimulate the secretion of CS by activating both alpha 2- and alpha 1-adrenoceptors in the hypothalamus.

The effects of chronic immobilization stress on the physiological responses of male rats were studied. The results indicate that the SP-like immunoreactivity (SPLIR) is diminished in the adrenals and pituitary after chronic stress. In vitro noradrenaline (NA) release from adrenals was increased. The i.p. administration of SP during the stress procedure normalized the increased NA release in vitro indicating that the catecholamine secretion may be influenced by SP. On the other hand, in demedullated animals the SPLIR in the pituitary was partly reduced and the blood pressure was increased. In such animals chronic stress resulted in an increase of SPLIR in the pituitary in comparison with nonstressed, demedullated animals, but was without effect on the blood pressure. It is concluded that exposure to SP and the resulting decrease of noradrenaline release may have a significant influence on the pituitary-adrenal responsiveness to stress.

Uptake by the isolated perfused sheep choroid plexus of labelled naturally occurring amino acids, and the analogue MeAIB (methyl amino isobutyric acid) was measured using the single-pass, indicator dilution method. The uptake (Umax) of natural amino acids at the blood face of the choroid plexus, relative to the extracellular marker mannitol, ranged between 26 and 47% when using a saline perfusate. However, when the perfusion fluid was changes to one containing whole blood, uptake of the leucine, phenylalanine, proline, aspartate glutamate and lysine were significantly reduced with Umax now between -1.6 and 19.5%. In contrast the uptake of alanine, glutamine and glycine remained high despite the change in perfusion fluid. All amino acids, which showed uptake from the blood, also demonstrated self-inhibition when an additional 1 mM of the same unlabelled amino acid was added to the perfusion fluid. This indicates saturation of a carrier-mediate uptake process. There was no detectable uptake of the amino acid analogue, MeAIB during perfusion with either medium, confirming the absence of the "A" type amino acid carrier system for which this analogue is specific.

The binding parameters of muscarinic antagonists in intact rat thymocytes were determined from competitive binding experiments with 3H-N-methylscopolamine (3H-NMS). The muscarinic antagonists inhibited binding of 3H-NMS in a dose-dependent manner. Non-linear regression analysis of the displacement curves indicated the presence of two affinity states for the muscarinic compounds. The beta-blocking agents R-propranolol, S-propranolol and alprenolol inhibited the binding of 3H-NMS to one, low affinity binding site on rat thymic lymphocytes. The ganglionic blocking substance hexamethonium did not affect the binding of 3H-NMS. The results indicate the presence of two binding sites for the radioligand on rat thymocytes, of which only one is specific for muscarinic receptor antagonists.

Our experiments showed that a continuous chronic administration of norepinephrine (NE) to rats for 20 h by means of subcutaneously implantable retard tablets, led to a highly significant epinephrine(E) depletion of the adrenal medulla during normoglycemia. The rise of free plasma NE was accompanied by increased free plasma E values at 12 hours. At this time the liver contents of glycogen and free intracellular glucose showed their most pronounced decrease. At 12 and 20 hours both liver glycogen and medullar E values were very low. To check a possible causal relationship between those two events another experiment was performed in which the breakdown of liver glycogen should be inhibited. NE treated rats were force fed with 50% glucose solution 9 h after tablet implantation. This resulted in only mild glycogen depletion, which was no more able to trigger E liberation from the medulla. Therefore we conclude that pronounced liver glycogen depletion possesses a triggering ability for medullar E output by which hypoglycemia could be prevented.

Dynamic studies of growth hormone (GH) secretion were performed in two patients with ectopic GHRH syndrome. Patient 1 (female, 33 years old) had a growth hormone releasing hormone (GHRH) producing carcinoid of the lung with clinical features of acromegaly while patient 2 (50 years old male) had small cell carcinoma of the lung without acromegaly. Insulin hypoglycemia stimulated GH secretion in both patients (i.e. from a basal level of 10 mU/l to 48 mU/l in patient 1, while the respective values in patient 2 were 5 mU/l and 61 mU/l), TRH acutely stimulated GH in both patients. Synthetic GHRH 1-29 (KABI) i.v. bolus 100 micrograms did not stimulate GH release in either patient (i.e. basal GH 14 mU/l and peak 18 mU/l (patient 1); basal GH 4.6 mU/l and peak 8.8 mU/l (patient 2). It is concluded that: 1. prolonged pituitary exposure to GHRH is associated with chronic GH hypersecretion with or without clinical acromegaly; 2. GH response to TRH may be mediated at the pituitary level and results from prolonged exposure to GHRH; 3. the discordant response of GH after GHRH and insulin induced hypoglycemia might suggest the involvement (at least partially) of somatostatin in the mechanism of GH release after hypoglycemia and after GHRH.

The effect of differences in sympathoadrenomedullary and pituitary-adrenocortical responses of individual animals to 35% hemorrhage on severity of shock induction has been studied in unanesthetized unrestrained rats by measuring plasma concentrations of adrenaline (A), noradrenaline (NA), corticosterone (CS) and adrenocorticotropin (ACTH). The responses of A, CS and ACTH were related to the decrease of blood volume and mean arterial pressure (MAP), whereas plasma NA remained unchanged. Higher susceptibility to blood loss was characterized by more pronounced hemorrhage-induced increase in blood lactate concentration and plasma enzyme activities as well as lethal outcome of hemorrhagic shock. In animals with irreversible hemorrhagic shock, enhanced catecholamine secretion and reduced ACTH release was observed. Furthermore, a revealed direct correlation between A and blood lactate concentration and plasma enzyme activities (aspartate aminotransferase, isocitric dehydrogenase, creatine kinase, lipase and glutathione-S-transferase) may indicate its possible participation in the mechanism of shock induction. In contrast, an inverse relationship of plasma CS to the indicators of shock severity was demonstrated. In conclusion, non-optimal neuroendocrine regulation of cardiovascular adjustments to hemorrhage in shock-prone animals might cause an exaggerated compensatory activation of adrenomedullary catecholamine secretion, which in turn has been shown to exert deleterious vascular and metabolic effects. The mechanisms responsible for reduced ACTH secretion in shock-prone animals remain to be established.

The effects of thymic hormone thymosin (fraction 5) and tactivin on the adrenal glucocorticoid function were compared in BALB/c mice. An elevation in plasma corticosterone level was found 3 h after i.p. injection of thymosin (1 microgram/mouse) which was possibly caused by an activation of neuroendocrine structures. This appeared plausible because the pretreatment with dexamethasone (10 micrograms/mouse) abolished the effect of thymosin. In contrast, tactivin produced a decrease in plasma corticosterone if administered to mice with high basal level of the hormone. Tactivin added at doses from 0.00064-2 micrograms/ml together with ACTH (1.6 microIU/ml) to isolated adrenal cells hindered the stimulatory influence of ACTH on the production of corticosterone by the adrenal cells. Thus, the thymic hormone thymosin and tactivin showed opposite influences on the adrenal glucocorticoid function which appeared to be mediated through different mechanisms.

The period of elimination of tricyclic antidepressant amitriptyline was studied both in plasma and erythrocytes and the influence of the preparation of blood element samples on the elimination of residual antidepressant was examined. Also the effect of stress on antidepressant level was studied. Amitriptyline was not found in plasma 14 days after its withdrawal, while at the same time its levels in erythrocytes were still well measurable. Repeated washing of erythrocyte membranes did not eliminate the residual drug completely. Demethylase activity was found to be enhanced by stress. It is suggested that all results of antidepressant binding studies may be influenced by residual drug concentration in tissues. Interindividual variability may be caused by various intensity of stress mechanisms related to depressive disorders.