Endocrinologia experimentalis最新文献

A lower level of beta-endorphin (BE) was demonstrated in patients with both acute and chronic duodenal ulcer (P less than 0.01), while the basal level of bombesin (BO) in such patients did not differ from that in healthy subjects. The basal pancreatic polypeptide (PP) level was higher in both groups of patients, primarily in those with acute ulcer (P less than 0.01). A significantly negative correlation (P less than 0.001) between the levels of BE and BO, and between those of BE and PP, was found in healthy subjects. Similar interrelation was absent in ulcer patients.

Atrial natriuretic factor (ANF) is widely distributed in the preoptic area and the hypothalamus, it is present there both in cell bodies and nerve terminals. Effect of experimental alterations in the salt and water balance was examined on preoptic-hypothalamic ANF levels measured in ten microdissected nuclei. Immunohistochemical analysis was also performed to confirm radioimmunological results. Following interventions were performed in adult male rats: adrenalectomy (5 days), daily 0.9% NaCl, aldosterone (5 micrograms/100 g) and dexamethasone (2 micrograms/ml drinking water) treatments in both intact and adrenalectomized groups, and in rats with diabetes insipidus (Brattleboro rats) and DOC-salt hypertension. Although no appreciable alterations were observed in the intensity of ANF-like immunoreactivity in sections of the preoptic-hypothalamic region, ANF levels altered markedly in the periventricular structures (organum vasculosum laminae terminalis, preoptic and periventricular nuclei). Little or no changes were measured in ANF levels of other hypothalamic nuclei (except the perifornical nucleus). Adrenalectomy depleted ANF levels which were restored by NaCl drinking. Aldosterone elevated ANF concentrations both in intact and adrenalectomized animals while dexamethasone treatment was without any significant effect on ANF levels in the periventricular preoptic nucleus. Diabetes insipidus or DOC-salt hypertension had little or no effect on ANF levels in this brain area. Unchanged ANF concentrations were also measured in the vasopressin-containing supraoptic nucleus following adrenalectomy or in diabetes insipidus rats.

In 49 healthy subjects during 2 h exercise on bicycle ergometer four variants of changes of beta-endorphin level were observed: 1. an increase during first 30 min followed by a decreased below initial values; 2. biphasic increase (peak values at the 30th and 120th min); 3. increase only during the 2nd h of exercise; 4. decrease during the whole period of exercise. For trained subjects the most common was the biphasic increase, for untrained ones--the overall decrease.

Neuropeptide Y (NPY) is a peptide originally isolated from porcine brain and subsequently shown to be widely distributed in the body of several species, including man. Neuropeptide Y is a circulating peptide; however, blood levels were higher in portal than peripheral blood of anesthesized rats. Earlier studies in ovariectomized and intact male rats have shown that intraventricular injection of NPY inhibits release of growth hormone (GH) and luteinizing hormone (LH) without producing significant modification of plasma follicle stimulating hormone (FSH) and thyrotropin stimulating hormone (TSH). In the male low doses of NPY elevate prolactin (PRL) whereas high doses suppress its release. To assess the physiologic significance of these actions, we injected a highly specific anti-NPY serum (aNPY) into the third cerebral ventricle (3V) of unrestrained male, ovariectomized, and ovariectomized, estrogen progesterone blocked rats and measured plasma GH, PRL, LH and TSH by blood sampling via indwelling jugular catheters. Third ventricular injection of aNPY (2 microliters of 1:10 dilution) caused a significant elevation of plasma GH levels after 3 and 4 h compared to the values in NRS (1:10)-injected rats. To determine if these changes were due to alterations in pituitary responsiveness to somatostatin, the rats were injected intravenously with a challenge dose of somatostatin (0.5 microgram) 2 h after previous injection of aNPY or NRS, and blood samples were taken every 10 min for 30 min. The responses did not differ in both groups which indicated that the antiserum was not acting directly on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions of radiolabelled circulating neuroactive peptides: enkephalin-leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood-cerebrospinal fluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood-cerebrospinal fluid barrier by a saturable mechanism. On the other hand, a non-saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinal fluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system.

We performed 113 new treatments in 98 patients (pts) (69 females and 27 males), 41 with macroprolactinoma, 26 with microprolactinoma, 5 with empty sella and 26 with idiopathic hyperprolactinemia. Parlodel LA was administered in 31/113, Parlodel LAR in 51/113, Parlodel SRO in 24/113 and Cabergoline in 8/113. In each pt the clinical effect, PRL plasma level CT-scan and visual field examination were monitored. PRL plasma levels normalized in 84/98 pts. In 13/41 macroadenoma pts a complete disappearance of the adenomatous mass was observed at CT-scan after 0.5-3 years' oral bromocriptine or Parlodel LAR therapy. The clinical features normalized in most of the pts. In conclusion, the new long acting dopamine agonists may represent the future of the management of hyperprolactinemic states because of their effectiveness, tolerability and good compliance.

Previous studies have suggested the subfornical organ (SFO) to be the CNS site at which circulating angiotensin (ANG) acts to influence a variety of regulatory control mechanisms. We have utilised electrophysiological techniques: 1. to examine the neural connections through which the SFO exerts such control over hypothalamic regulatory control centres; 2. to investigate the responsiveness of neurons in a second circumventricular organ, the area postrema (AP), to circulating peptides. In accordance with previous endocrine studies we have demonstrated excitatory influences of SFO efferents on hypothalamic neurosecretory neurons putatively identified as vasopressin, oxytocin, CRH, and LHRH secreting. In addition systemic ANG increased the activity of the former three groups of these neurons, an effect which was abolished by destruction of the SFO. Single unit recordings from AP neurons have demonstrated subpopulations of cells in this regions to be sensitive to either circulating ANG or changes in blood pressure.

The effects of the classical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-induced plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) release were investigated. Male Wistar rats provided with a permanent heart catheter and a permanent stomach catheter were used. Placement of rats into an unfamiliar cage (novel environment stress; NES), that elevated CS, NA and A, was used as a stressor. Acute administration of CDP (1-27 mg/kg) produced dose-related increases in basal plasma CS secretion but was without effect on basal NA content. The largest dose of CDP caused a slight short-term A elevation. The CDP effect on basal CS secretion tolerated with repeated drug treatment and was completely blocked after acute pretreatment with the BDZ receptor antagonist flumazenil. Acute treatment with BUSP (2-20 mg/kg) caused a marked and dose dependent increase in the plasma levels of A, NA and CS. A medium dose of CDP (9 mg/kg) attenuated the NES-induced CS and A elevations. A high dose of CDP (27 mg/kg), that elevated basal CS release, prevented a further CS increase by NES and inhibited the NA and A response to NES. BUSP (2 or 20 mg/kg) was not effective in attenuating the NES-elicited rise of CS, NA and A. However, the 20 mg/kg dose of BUSP actually enhanced the NES-induced A response. In conclusion, BUSP did not show the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the findings suggest that CDP and BUSP differentially affect the mechanisms controlling CS, NA and A release during basal and stress conditions.

Putative sleep substances were infused either singly or in combination into the third ventricle of freely behaving male rats for 10 h nocturnal period. The nocturnal amount of slow wave sleep (SWS) and paradoxical sleep (PS), and the number and duration of their episodes were compared to those of the previous night under saline infusion. The single administration revealed that each substance elicited partially differential and partially common sleep-modulatory activity. SWS was enhanced by the d-type of di-1-methylheptyl-2,5-dioxocyclohexane-1,4-dicarboxylate (d-DOC, 2.3 nmol), delta-sleep-inducing peptide (DSIP 2.5 nmol), deoxyuridine (0.1 nmol), muramyl dipeptide (MDP, 2.0 nmol), and prostaglandin D2 (PGD2, 0.36 nmol). Cytidine (10 pmol) increased the number of SWS episodes and reduced their duration, whereas deoxyguanosine (10 pmol) prolonged the duration. Deoxycytidine (10 pmol) and the 1-type of DOC (0.25 nmol) enhanced PS. Uridine (10 pmol) enhanced both SWS and PS. The simultaneous or sequential administration of DSIP, MDP and uridine resulted in a combination-dependent or sequence-dependent change in sleep-waking dynamics, which was quite different from the time-course sleep-modulation induced by the single administration of each substance. The results suggest that co-circulating sleep substances might interact at least in part, either synergistically or antagonistically, on the sleep-regulatory mechanism.

Protein formation in the anterior pituitary was investigated in vitro in thyroidectomized (TX) and/or adrenalectomited (AX) rats treated with a single dose of 100 micrograms/100 g of 3,5,3'-triiodothyronine (T3) and/or with a single dose of 10 micrograms/100 g of dexamethazone (DEX) 12 h before sacrifice. Male Wistar rats of a specific pathogen free colony 6 weeks after TX and/or AX receiving 1% calcium chloride and/or saline after surgery were used in the experiments. Non-pooled anterior pituitaries (in acellular condition) complemented with all essential amino acids, CPK, creatine phosphate in a HEPES buffer containing potassium acetate, magnesium acetate and dithiothreitol, were incubated with 35S-methionine at 28 degrees C for 10 or 40 min. The reaction was stopped by EDTA followed by RNAase plus DNAase treatment and the samples were analyzed for total 35S-methionine incorporation or by SDS 12.5% polyacrylamide gel slab electrophoresis (PAGE). As compared to intact rats (100%), TX and/or AX caused a significant diminution of the total 35S-methionine incorporation into protein ranging from 33% to 68% that may be easily restored to 107% by T3 plus DEX treatment. PAGE analysis reflects an appreciable relation between T3 administration and 21.5 kDa protein (growth hormone) formation in the anterior pituitary. In addition, the effect 5,5'-diphenylhydantoine (DPH) on 35S-methionine incorporation in relation to T3 nuclear specific binding was investigated. The data suggest that the decreased protein synthesis de novo is due to a significant diminution of T3 specific binding to nuclear receptors in the anterior pituitary.