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21.
22.
Anna Spada†‡ Farzin Reza-Elahi†‡ rea Lania†‡ Atanasio Pandiella†† Monique Bassetti†† Nicoletta Bazzoni† Paloma Gil de Alamo† Giovanni Faglia† 《Journal of neuroendocrinology》1991,3(1):51-56
The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca2+ concentration, [Ca2+)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca2+]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca2+ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca2+ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca2+]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca2+]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca2+]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca2+]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca2+]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca2+]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca2+]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca2]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide. 相似文献
23.
Various neural factors are involved in the suckling-induced increase in serum growth hormone (GH) levels in neonatal rats, and, in the present study the serotonergic, cholinergic, somatostatin and GH-releasing hormone (GHRH) systems were investigated. The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP) and the 5-HT receptor agonist quipazine maleate stimulated serum GH levels in 2-day-old rat pups separated from their mothers for 6 h. The increase in serum GH during suckling was further elevated by 5-HTP. The 5-HT antagonist cyproheptadine decreased serum GH levels in separated 2-day-old pups, and although it reduced the amplitude of the suckling-induced increase in serum GH concentration, it did not alter the increase in serum GH on a percentage basis. The effect of the cholinergic muscarinic antagonist atropine sulfate (ATR) was similar to that of cyproheptadine. Moreover, in separated pups, ATR prevented the increase in serum GH induced by 5-HTP. In contrast with 2-day-old pups, ATR completely eliminated the suckling-induced release of GH in 10-day-old rats. However, ATR failed to prevent GH release induced by the α2-adrenergic agonist clonidine HCI in 10-day-old male pups. While thyrotropin-releasing hormone increased serum GH levels, rat GHRH failed to alter serum GH levels either in separated or in suckled 2-day-old rat pups. Immunoneutralization for rat GHRH eliminated the increase in serum GH induced by clonidine HCI in 10-day-old pups, but (on a percentage basis) failed to prevent the GH-increasing effect of suckling in 2-day-old pups. While somatostatin failed to significantly decrease serum GH in separated 2-day-old pups, it effectively decreased serum GH levels in 2-day-old pups which were suckled. Cysteamine, which depletes hypothalamic somatostatin, increased serum GH in separated 2-day-old pups, and further increased the suckling-induced levels of serum GH. Cysteamine partially prevented the GH-decreasing effect of ATR. The present findings suggest that 1) the serotonergic and cholinergic systems are involved in the regulation of GH secretion as early as day 2 postpartum; 2) the serotonergic and cholinergic systems modulate the basal, and do not modulate the suckling-induced levels of serum GH; 3) the serotonergic system may exert its stimulatory influence on GH secretion only in the presence of a functional muscarinic cholinergic system; 4) the cholinergic system, at least in part, stimulates GH secretion via a cysteamine-sensitive system (probably by inhibiting somatostatin); 5) the cholinergic system is not functionally coupled with the α2-adrenergic system, which stimulates GH secretion via rat GHRH; 6) since in 10-day-old pups clonidine HCI was effective only in males, while suckling was effective in both sexes, the α2-adrenergic system is not involved in the suckling-induced increase of serum GH; and finally 7) neither somatostatin nor rat GHRH seem to be involved in the suckling-induced changes in serum GH. The findings are consistent with the hypothesis that the high circulating GH levels in the neonatal rat are due to alternative GH-releasing factors, perhaps thyrotropin-releasing hormone or γ-aminobutyric acid. The neurohumoral mediator of the suckling-induced GH release in neonatal rats remains to be identified. 相似文献
24.
LI Wei-yong LI Qian QIAO Jian DENG Jun-gang ZHANG Ying 《中国临床药理学与治疗学》2007,12(10):1182-1183
AIM: To determine the safety, tolerability and pharmacokinetic parameters of a new drug recombinant human parathyroid hormone [ rhPTH (1-84)] in healthy male Chinese subjects. METHODS: domly divided Thirty-six healthy male volunteers were rangroups received into 3 groups. The volunteers in these single subcutaneous injection of rhPTH ( 1-84) in a dosage of 1, 2 and 4 μg/kg respectively. Blood samples were obtained before and after administration within 24 hours. The rhPTH concentrations in sennn were determined by enzyme linked immunosorbent assay (ELISA). The pharmacokinetic parameters determined with use of standard noncompartmental analysis were the maximum serum concentration ( Cmax ), the time to attain that concentration ( tmax ), and the area under the serum concentration-time curve up to 24 hours( AUC0-24 ) and up to infinity (AUC0-∞). Dose proportionality of pharmacokinetic parameters (AUC, Cmax of every volunteer of each dosage and A UC was computed from log transformed data) and was examined by mean of analysis of variance (ANOVA) using SPSS software package. In the study, subjects' symptoms, objective signs, and vital signs, including blood pressure, heart rate, respiratory rate and body temperature, were checked and 12-lead electrocardiography was recorded before and after drug administration within 24 hours. Routine laboratory tests, including hematology, blood biochemistry, serum electrolyte, and urinalysis, were performed before and after drug administration within at 24 hours.[第一段] 相似文献
25.
The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity. 相似文献
26.
Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P<0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P<0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P<0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.This study was presented in part at the 76th Annual Meeting of the Endocrine Society, Anaheim, CA, USA, June 1994. 相似文献
27.
Stewart Shapiro Dimitris N. Tatakis Dr. Rosemary Dziak 《Calcified tissue international》1990,46(1):60-62
Summary Tumor necrosis factor α (10−10–10−8M) had no effects on cyclic AMP production by the osteoblastic osteosarcomal cells, Saos-2 and G292, or normal rat calvarial
cells. The cytokine did, however, inhibit the parathyroid hormone (PTH)-induced effect on cyclic AMP in the Saos-2 and normal
rat osteoblastic cells. This inhibitory effect did not occur on prostaglandin E2-induced cyclic AMP increases in the osteoblastic cells. Interleukin-1 (10 U/ml −100 U/ml) did not produce any effect on basal
levels or PTH-induced cyclic AMP increases in these cells. 相似文献
28.
Effects of androgen treatment in impotent men with normal and low levels of free testosterone 总被引:1,自引:0,他引:1
Cesare Carani M.D. Dante Zini M.D. Augusto Baldini M.D. Luciano Della Casa M.D. Anna Ghizzani M.D. Paolo Marrama M.D. 《Archives of sexual behavior》1990,19(3):223-234
The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimun serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens. 相似文献
29.
促甲状腺素释放激素类似物YM14673对小鼠学习记忆的影响 总被引:1,自引:0,他引:1
采用小鼠跳台法评价促甲状腺素释放激素类似物YM14673(ip1mg·kg-1)对正常成年小鼠被动回避学习记忆成绩的影响.结果表明YM14673对东莨菪碱,氯霉素和乙醇造成的小鼠记忆获得,巩固及再现障碍均有明显的改善作用. 相似文献
30.
为了探讨增产菊胺酯引起小鼠精了生成障碍的可能机理,本文研究了增产菊胺酯对雄性小鼠卵泡刺激素(FSH)、黄体生成素(LH)及睾酮(T)的影响。小鼠经口染毒,隔天一次,连续10次,第35天处死。检验因清FSH、LH没有明显变化,而睾丸组织睾酮含量出现剂理依赖性降低,高剂量组与对照组比较有显著性差异(P〈0.05),结果表明,增产菊胺酯不影响FSH、LH,而影响T的合成和分泌。这可能是增产菊胺酯对小鼠精 相似文献