• 【甲状腺激素的核“受体”的特异性如何?】 复制标题 收藏 收藏
    DOI:10.1038/257018a0 复制DOI
    作者列表:Tata JR
    BACKGROUND & AIMS: :The presence of "high-affinity-saturable" binding sites for thyroid hormones of similar characteristics not only in isolated nuclei but in all the major extranuclear cellular components, as well as the failure of cytosol to promote nuclear binding, invalidates the analogy with steroid hormone receptors and necessitates a more critical assessment of the physiological relevance of current approaches to binding of thyroid hormone in vitro nuclear preparations.
    背景与目标: :不仅在分离的细胞核中,而且在所有主要的核外细胞成分中,具有类似特征的甲状腺激素的“高亲和力饱和”结合位点的存在,以及胞质溶胶不能促进核结合,使类固醇类比无效激素受体,因此有必要对目前体外核制剂中结合甲状腺激素的方法的生理相关性进行更严格的评估。
  • 【老年癌症患者炎症标志物和激素的分析:一项描述性研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.exger.2019.110787 复制DOI
    作者列表:De Breucker S,Luce S,Njemini R,Bautmans I,Decoster L,Mets T,Pepersack T
    BACKGROUND & AIMS: :Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76-83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition.
    背景与目标: 晚期癌症与慢性炎症有关,尤其是高白介素6(IL-6)和各种水平的脂联素(瘦素和脂联素),而ghrelin抵消了瘦素在癌症诱发的厌食-恶病质综合征中的厌食作用。我们旨在了解一方面IL-6,脂肪因子和生长素释放肽血浆水平如何受到癌症的影响,另一方面又受老年癌症患者的年龄,虚弱和营养状况的影响。纳入年龄为79 [76-83]岁的99例患者。 66%患有癌症晚期,34%患有恶病质。百分之五十有营养不良的风险,百分之十有明显的营养不良。没有研究的变量与晚期或恶病质显着相关。在多元回归中,与年龄显着正相关的唯一参数是脂联素(p = 0.008)。尽管在我们的研究中脆弱性的患病率很高,但在多变量分析中,我们没有发现脆弱性(由G8评估)与IL-6,瘦素,脂联素或生长素释放肽的任何独立关联。我们观察到较低的白蛋白水平与较高的IL-6水平(p <0.0001)独立相关,但与MNA评分无关。然而,瘦素与BMI呈正相关(p <0.0001),证实了瘦素与肥胖之间的关系仍然存在,即使在老年癌症患者中也是如此。最后,高IL-6水平与更高的死亡率相关(p = 0.027)。总之,在老年癌症患者中,IL-6,瘦素,脂联素和生长素释放肽与癌症晚期或癌症诱发的恶病质无关,但它们与人体测量因素和身体组成显着相关。
  • 【敏感的生物测定法测定黑素激素,使用分离的果黑素细胞。】 复制标题 收藏 收藏
    DOI:10.1016/0016-6480(88)90101-3 复制DOI
    作者列表:Negishi S,Kawazoe I,Kawauchi H
    BACKGROUND & AIMS: :Melanophore-stimulating hormones (MSHs) from chum salmon cause pigment dispersion in isolated melanophores of medaka, a teleost. The in vitro medaka melanophore bioassay that responded to light with pigment dispersion and to the dark with pigment aggregation was utilized for measuring the activity of melanotropic hormones. alpha-MSH I was the most potent melanophore-dispersing agent tested. The minimal dose for the induction of pigment dispersion was 10(-15) M alpha-MSH I, 10(-13) M N-des-acetyl(Ac)-alpha-MSH, and 10(-11) M beta-MSH I, respectively. The melanosome-dispersing activity of beta-MSH I was enhanced about 40% by salmon N-acetyl-endorphin I (N-Ac-EP). The results suggest that N-Ac-EP may act as an enhancer for the activity of certain MSHs. The present bioassay provides a unique method for determining the biological activity of melanotropic peptides.
    背景与目标: :来自鲑鱼的促黑素刺激激素(MSH)导致色素分散在硬骨鱼(Medaka)的孤立黑素细胞中。利用体外对色素分散的光和对色素凝集的黑暗作出反应的medaka黑色素生物测定法来测定促黑素激素的活性。 alpha-MSH I是测试过的最有效的黑色素分散剂。诱导颜料分散的最小剂量是10(-15)M alpha-MSH I,10(-13)M N-des-乙酰基(Ac)-alpha-MSH和10(-11)M beta-MSH我分别。鲑鱼N-乙酰-内啡肽I(N-Ac-EP)将β-MSHI的黑素体分散活性提高了约40%。结果表明,N-Ac-EP可能充当某些MSHs活性的增强剂。本生物测定法提供了确定黑素肽的生物活性的独特方法。
  • 【甲状腺激素减少了默里河短颈龟(Emydura macquarii)的潜伏期,而没有发育或代谢成本。】 复制标题 收藏 收藏
    DOI:10.1086/689744 复制DOI
    作者列表:McGlashan JK,Thompson MB,Van Dyke JU,Spencer RJ
    BACKGROUND & AIMS: :Metabolic processes are affected by both temperature and thyroid hormones in ectothermic vertebrates. Temperature is the major determinant of incubation length in oviparous vertebrates, but turtles can also alter developmental rate independent of temperature. Temperature gradients within natural nests cause different developmental rates of turtle embryos within nests. Despite temperature-induced reductions in developmental rate, cooler-incubated neonates often hatch synchronously with warmer siblings via metabolic compensation. The physiological mechanisms underlying metabolic compensation are unknown, but thyroid hormones may play a critical role. We applied excess triiodothyronine (T3) to developing eggs of Murray River short-necked turtle (Emydura macquarii)-a species that exhibits metabolic compensation and synchronous hatching-to determine whether T3 influences developmental rate and whether changes to incubation period incur metabolic costs. We measured heart rate, oxygen consumption and incubation period of eggs, and morphology and performance of hatchlings. Embryos that were exposed to T3 pipped up to 3.5 d earlier than untreated controls, despite no change in total metabolic expenditure, and there were no treatment differences in hatchling morphology. Hatchlings treated with T3 demonstrated similar righting ability to hatchlings from the control groups. Exposure to T3 shortens incubation length by accelerating embryonic development but without statistically increasing embryonic metabolism. Thus, T3 is a mechanism that cooler-incubated reptiles could use to accelerate their development to allow synchronous hatching with their warmer clutch mates but at little or no metabolic cost. Thus, metabolic compensation for synchronous hatching may not be metabolically expensive if T3 is the underlying mechanism.
    背景与目标: :热代谢脊椎动物的代谢过程受温度和甲状腺激素的影响。温度是卵生脊椎动物孵化时间的主要决定因素,但是乌龟也可以独立于温度而改变发育速度。天然巢穴中的温度梯度会导致巢穴中龟胚发育的速率不同。尽管温度导致发育速度降低,但较冷孵化的新生儿通常会通过代谢补偿与较热的兄弟姐妹同时孵化。代谢补偿的生理机制尚不清楚,但甲状腺激素可能起关键作用。我们将过量的三碘甲腺氨酸(T3)应用于表现出代谢补偿和同步孵化的墨累河短颈龟(Emydura macquarii)的卵的发育,以确定T3是否影响发育速度以及潜伏期的变化是否引起代谢成本。我们测量了心率,耗氧量和卵的潜伏期,以及孵化的形态和性能。暴露于T3的胚胎比未处理的对照组早了3.5 d,尽管新陈代谢的总支出没有变化,并且在孵化形态上没有差异。用T3处理的小鱼与对照组的小鱼表现出相似的扶正能力。暴露于T3可以通过加速胚胎发育而缩短孵化时间,但在统计学上不会增加​​胚胎代谢。因此,T3是一种机制,低温孵化的爬行动物可以用来加速它们的发育,以便与温暖的离合器伴侣进行同步孵化,而代谢成本却很少或没有。因此,如果T3是潜在的机制,则同步孵化的代谢补偿可能不会在代谢上昂贵。
  • 【原始研究:短跑和力量训练对糖调节激素的影响:老年的影响。】 复制标题 收藏 收藏
    DOI:10.1177/1535370216662711 复制DOI
    作者列表:Sellami M,Ben Abderrahman A,Kebsi W,De Sousa MV,Zouhal H
    BACKGROUND & AIMS: :The aim of this study was to examine the effect of high-intensity sprint and strength training (HISST) on glucoregulatory hormones in young (20 years) and middle-aged (40 years) men. Thirty-six moderately trained men participated as volunteers in this study. After medical examination, eligible subjects were randomly assigned to one of four groups according to their age: a young training group (21.3 ± 1.3 yrs, YT, n = 9), a young control group (21.4 ± 1.7 yrs, YC, n = 9), a middle-aged training group (40.7 ± 1.8 yrs, AT, n = 9), and a middle-aged control group (40.5 ± 1.8 yrs, AC, n = 9). YT and AT participated in HISST for 13 weeks. Before and after HISST, all participants performed the Wingate Anaerobic Test (WAnT). Blood samples were collected at rest, after warm-up (50% VO2max), immediately post-WAnT, and 10 min post-WAnT. Before HISST, we observed significantly higher (P < 0.05) glucose concentrations in AT (5.86 ± 0.32 mmol.L-1) compared to YT (4.24 ± 0.79 mmol.L-1) at rest, and in response to WAnT (6.56 ± 0.63 mmol.L-1 vs. 5.33 ± 0.81 mmol.L-1). Cortisol levels were significantly higher (P < 0.05) in AT than in YT in response to WAnT (468 ± 99.50 ng.mL-1 vs. 382 ± 64.34 ng.mL-1). Catecholamine levels measured at rest and in response to WAnT rose in a similar fashion. After HISST, this "age effect" disappeared at rest and in response to exercise in the trained groups (YT and AT). Changes in hormone concentrations with intense training are due to adaptive changes in various tissues, especially in the skeletal muscle and liver in trained subjects. HISST may, at least in part, counteract the negative "age effect" on glucose metabolism.
    背景与目标: :这项研究的目的是检查高强度的短跑和力量训练(HISST)对年轻(20岁)和中年(40岁)男性的糖调节激素的影响。三十六名受过中等训练的男人作为志愿者参加了这项研究。医学检查后,将符合条件的受试者根据年龄随机分为四组之一:一个年轻的训练组(21.3%±1.3岁,YT,n = 9),一个年轻的对照组(21.4%±1.7岁,YC,nC = n = 9)。 9),一个中年训练组(40.7±±1.8岁,AT,n = 9)和一个中年对照组(40.5±±1.8岁,AC,n = 9)。 YT和AT参加了HISST,为期13周。在HISST之前和之后,所有参与者都进行了Wingate无氧测试(WAnT)。预热(50%VO2max)后,静息后,静息后和静息后10分钟,静息时收集血样。在HISST之前,我们观察到静息时AT(5.86±±0.32 mmol.L-1)中的葡萄糖浓度(4.24±±0.79 mmol.L-1)显着更高(P <0.05),并且对WAnT(6.56±±)有反应0.63 mmol.L-1对5.33(±0.81 mmol.L-1)。响应WAnT,AT中的皮质醇水平显着高于YT(P <0.05)(468±99.50ng.mL-1 vs. 382±64.34ng.mL-1)。静息时和对WAnT的反应中测得的儿茶酚胺水平以类似方式上升。在HISST之后,这种“年龄效应”在休息时以及在训练有素的人群(YT和AT)对运动的反应中都消失了。激烈训练中荷尔蒙浓度的变化是由于各种组织的适应性变化,特别是受过训练的受试者的骨骼肌和肝脏中的变化。 HISST可以至少部分抵消对葡萄糖代谢的负面“年龄效应”。
  • 【性激素类固醇激素与多族裔妇女的骨折:妇女健康倡议研究(WHI)。】 复制标题 收藏 收藏
    DOI:10.1210/jc.2016-3589 复制DOI
    作者列表:Cauley JA,Danielson ME,Jammy GR,Bauer DC,Jackson R,Wactawski-Wende J,Chlebowski RT,Ensrud KE,Boudreau R
    BACKGROUND & AIMS: Context:We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. Design and Setting:We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone. Results:In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03. Conclusions:Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.
    背景与目标: 背景:我们假设内源性类固醇与骨折风险相关,而与种族/民族无关。
    设计与设置:我们在前瞻性妇女健康倡议观察研究中进行了嵌套的病例对照研究。平均8.6年内,在381名黑人,192名西班牙裔,112名亚洲裔和46名美国原住民女性中发现了非脊柱骨折事件。随机抽取400名经历骨折的白人妇女作为样本。根据病例选择一个对照,并根据年龄,种族/民族和抽血日期进行匹配。使用基线禁食血清测量可利用的雌二醇(BioE2),可利用的睾丸激素(BioT)和性激素结合球蛋白(SHBG)。条件逻辑回归模型计算了激素三分位数之间骨折的比值比(OR)和95%置信区间(CI)。
    结果:在多变量和种族/种族调整的模型中,较高的BioE2(> 8.25 pg / mL)和较高的BioT(> 13.3 ng / dL)与骨折风险降低相关(OR,0.65; 95%CI,0.50至0.85 ; P趋势= 0.001,OR为0.76; 95%CI为0.60至0.96; P趋势= 0.02)。种族/种族与BioE2或BioT之间的相互作用项并不显着。 SHBG与骨折风险之间没有关联。在按种族/族裔分层的模型中,白人女性(OR,0.56; 95%CI,0.36至0.87)和黑人女性(OR,0.61; 95%CI,0.39至0.96)中较高的BioE2与较低的骨折风险相关)。只有黑人女性的BioT较高与骨折风险显着降低有关(OR为0.65; 95%CI为0.43至1.00),P趋势= 0.03。
    结论:血清BioE2和BioT与老年妇女的骨折风险相关,而与种族/民族无关,并且与确定的骨折危险因素无关。
  • 【在虹鳟鱼的成长期和肥育阶段,n-3 LC-PUFA的沉积效率和食欲调节激素受膳食脂质来源的调节。】 复制标题 收藏 收藏
    DOI:10.1007/s10695-013-9868-5 复制DOI
    作者列表:Francis DS,Thanuthong T,Senadheera SP,Paolucci M,Coccia E,De Silva SS,Turchini GM
    BACKGROUND & AIMS: :Largely attributable to concerns surrounding sustainability, the utilisation of omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in aquafeeds for farmed fish species is an increasingly concerning issue. Therefore, strategies to maximise the deposition efficiency of these key health beneficial fatty acids are being investigated. The present study examined the effects of four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma concentrations of the appetite-regulating hormones, leptin and ghrelin, during the grow-out and finishing phases in rainbow trout culture. Minimal detrimental effects were noted in fish performance; however, major modifications were apparent in tissue fatty acid compositions, which generally reflected that of the diet. These modifications diminished somewhat following the fish oil finishing phase, but longer-lasting effects remained evident. The fatty acid composition of the alternative oils was demonstrated to have a modulatory effect on the deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved in appetite regulation, growth and feed intake during both the grow-out and finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to 'spare' the catabolism of n-3 LC-PUFA and, as such, resulted in the highest retention of these fatty acids, ultimately highlighting new nutritional approaches to maximise the maintenance of the qualitative benefits of fish oils when they are used in feeds for aquaculture species.
    背景与目标: :很大程度上是由于人们对可持续性的关注,在养殖鱼类的水产饲料中利用富含ω-3长链多不饱和脂肪酸(n-3 LC-PUFA)的鱼油已成为一个日益引起关注的问题。因此,正在研究最大化这些对健康有益的关键脂肪酸的沉积效率的策略。本研究检查了四种基于蔬菜的膳食脂质来源(亚麻籽,橄榄油,棕榈和葵花籽油)对n-3 LC-PUFA的沉积效率以及食欲调节激素,瘦素和脂肪的循环血浆浓度的影响。 ghrelin,在虹鳟鱼养殖的成长期和育肥阶段。在鱼类生产中注意到了最小的有害影响。然而,在组织脂肪酸组成上的主要改变是明显的,这通常反映出饮食的改变。在鱼油精制阶段之后,这些修饰有所减弱,但更持久的效果仍然很明显。事实证明,替代油的脂肪酸组成对n-3 LC-PUFA的沉积效率以及在成长期和肥育阶段参与食欲调节,生长和采食的关键内分泌激素具有调节作用。 。特别是n-6 PUFA(葵花籽油饮食)似乎“浪费”了n-3 LC-PUFA的分解代谢,因此,这些脂肪酸的保留率最高,最终突出了新的营养方法,以最大限度地维持鱼油用于水产养殖种类饲料中时的定性益处。
  • 【绝经后及以后的生活中血清促性腺激素和类固醇激素的水平。】 复制标题 收藏 收藏
    DOI:10.1016/0378-5122(88)90024-2 复制DOI
    作者列表:Rozenberg S,Bosson D,Peretz A,Caufriez A,Robyn C
    BACKGROUND & AIMS: :Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.
    背景与目标: :研究了449名40岁及以上的女性随年龄增长而引起的血清促性腺激素和类固醇激素水平的变化,以调查这些激素之间的关系,甚至在生命的最晚时期也是如此。雌二醇(E2)和脱氢表雄酮硫酸盐(DHEA-S)的水平在50岁以后下降,此后保持较低水平。然而,尽管血清雌酮(E1),睾丸激素(T),δ4-雄烯二酮(A)和催乳激素(PRL)的浓度在50岁以后也开始下降,但随后又逐渐上升,实际上,对于E1。黄体生成素(LH)和促卵泡激素(FSH)在50岁以后上升,但是FSH保持升高,而LH在生命后期下降。皮质醇(F)在70岁以后显着增加。即使在60岁以后,雄激素和E1之间以及E2和LH之间也存在显着相关性。由于所研究人群的巨大异质性,尚无法推测这些观察的生理病理意义。但是,似乎雌激素对LH分泌的负反馈作用在生命的最后阶段仍然有效。
  • 【β-肾上腺素受体介导的大鼠主动脉松弛的调节受到内源性卵巢激素的调节。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Conde MV,Marín J,Fernandez-Criado C,Balfagón G
    BACKGROUND & AIMS: :The aim of this study was to assess the influence of the endogenous status of ovarian hormones on the relaxation induced by the beta-adrenoceptor agonists isoprenaline (isoproterenol) and dobutamine in thoracic aorta segments, precontracted with noradrenaline, from age-matched (13-week-old) virgin (oestrus) and ovariectomized (OVX) prepubertal female Wistar rats. Isoprenaline-induced relaxation was decreased in intact aortic segments from OVX rats compared with that in segments from oestrus rats. Relaxation was significantly reduced by endothelium removal, 1 micromol/l propranolol or 100 micromol/l N(G)-nitro-L-arginine methyl ester (L-NAME). The beta(1)-adrenoceptor agonist dobutamine induced less relaxation in intact arteries from oestrus rats than did isoprenaline, and dobutamine-induced relaxation was markedly less in intact segments from OVX compared with oestrus rats. This dobutamine-induced relaxation was abolished by endothelium removal, and reduced by 1 micromol/l propranolol, 100 micromol/l L-NAME or 1 micromol/l yohimbine. Cholera toxin (an activator of the stimulatory G-protein G(s)) caused relaxation in intact arteries from oestrus rats; this relaxation was decreased by both deprivation of ovarian hormones and endothelium removal. Forskolin (a direct activator of the catalytic subunit of adenylate cyclase) and sodium nitroprusside (a nitric oxide donor and cGMP-dependent vasodilator agonist) induced similar endothelium-independent relaxation in arteries from both oestrus and OVX rats. These results suggest that the relaxation elicited by endothelial beta-adrenoceptor activation in the rat thoracic aorta is impaired by deprivation of female ovarian hormones; this impairment is caused, at least in part, by decreases in both the endothelial release of NO and G(s) function.
    背景与目标: :这项研究的目的是评估年龄与年龄相匹配的人(13-周龄)处女(发情期)和卵巢切除(OVX)青春期前雌性Wistar大鼠。与发情期大鼠相比,OVX大鼠的完整主动脉节段中异丙肾上腺素引起的舒张降低。通过去除内皮,1μmol/ l普萘洛尔或100μmol/ l N(G)-硝基-L-精氨酸甲酯(L-NAME),松弛显着减少。与异丙肾上腺素相比,β(1)-肾上腺素能受体激动剂多巴酚丁胺在发情大鼠的完整动脉中引起的松弛较少,而在OVX的完整节段中,多巴酚丁胺引起的松弛与发情大鼠相比明显较少。多巴酚丁胺引起的松弛通过内皮去除而消除,并减少了1微摩尔/升普萘洛尔,100微摩尔/升L-NAME或1微摩尔/升育亨宾。霍乱毒素(一种刺激性G蛋白G(s)的激活剂)引起发情大鼠完整动脉的舒张。剥夺卵巢激素和去除内皮都减少了这种放松。福斯科林(腺苷酸环化酶催化亚基的直接激活剂)和硝普钠(一氧化氮供体和依赖cGMP的血管舒张激动剂)在发情期和OVX期大鼠的动脉中诱导了类似的内皮依赖性舒张作用。这些结果表明,剥夺雌性卵巢激素会损害由大鼠胸主动脉中的内皮β-肾上腺素受体激活引起的松弛。这种损害至少部分是由于内皮释放的NO和G(s)功能的降低所致。
  • 【性和性激素影响自发性高血压大鼠蛋白尿的发展和肾巨噬细胞浸润。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00429.2007 复制DOI
    作者列表:Sullivan JC,Semprun-Prieto L,Boesen EI,Pollock DM,Pollock JS
    BACKGROUND & AIMS: :There is a sex difference in hypertensive renal injury, with men experiencing greater severity and a more rapid progression of renal disease than women; however, the molecular mechanisms protecting against renal injury in women are unknown. The goal of this study was to determine whether sex hormones modulate blood pressure and the progression of albuminuria during the developmental phase of hypertension in male and female spontaneously hypertensive rats (SHR). Studies were also performed to examine how sex and sex hormones influence two major risk factors for albuminuria, overactivation of the renin-angiotensin system and oxidative stress. Blood pressure was measured by telemetry in gonad-intact and gonadectomized male and female SHR. Microalbumin excretion, measured over time, and macrophage infiltration were used to assess renal health. Male SHR had significantly higher blood pressures than female SHR, and gonadectomy decreased blood pressures in males with no effect in females. Male SHR displayed a gonad-sensitive increase in albuminuria over time, and female SHR had a gonad-sensitive suppression in macrophage infiltration. Female SHR had greater plasma ANG II levels and similar levels of renal cortical ANG II vs. levels shown in males but less AT(1)-receptor protein expression in the renal cortex. Female SHR also had a gonad-sensitive decrease in renal oxidative stress. Therefore, the renal protection afforded to female SHR is associated with lower blood pressure, decreased macrophage infiltration, and decreased levels of oxidative stress.
    背景与目标: :高血压肾损伤存在性别差异,男性比女性更严重,肾脏疾病进展更快;然而,保护女性防止肾脏损伤的分子机制尚不清楚。这项研究的目的是确定雄性和雌性自发性高血压(SHR)高血压形成阶段性激素是否能调节血压和蛋白尿的进展。还进行了研究以检查性激素和性激素如何影响蛋白尿的两个主要危险因素,即肾素-血管紧张素系统的过度活化和氧化应激。通过完整的性腺和性腺切除的男性和女性SHR,通过遥测法测量血压。随时间测量的微量白蛋白排泄和巨噬细胞浸润用于评估肾脏健康。男性SHR的血压明显高于女性SHR,性腺切除术可降低男性的血压,而对女性没有影响。男性SHR表现出蛋白尿随着时间的推移对性腺敏感的增加,而女性SHR对巨噬细胞浸润的性腺敏感的抑制作用。与男性相比,女性SHR具有更高的血浆ANG II水平和相似水平的肾皮质ANG II水平,但在肾皮质中的AT(1)-受体蛋白表达较少。女性SHR的肾脏氧化应激也对性腺敏感。因此,赋予女性SHR的肾脏保护作用与降低血压,减少巨噬细胞浸润和降低氧化应激水平有关。
  • 【在没有组织或尿激酶纤溶酶原激活剂或其1型抑制剂的情况下,骨吸收和对钙调节激素的反应。】 复制标题 收藏 收藏
    DOI:10.1002/jbmr.5650110814 复制DOI
    作者列表:Leloup G,Lemoine P,Carmeliet P,Vaes G
    BACKGROUND & AIMS: Plasminogen activators (PA) are implicated in cell migration and tissue remodeling, two components of the bone resorption processes. Using mice with inactivated tissue PA (tPA), urokinase PA (uPA), or type 1 PA inhibitor (PAI-1) genes, we evaluated whether these processes, or their stimulation by parathyroid hormone (PTH) or 1,25-dihydroxyvitamin (1,25[OH]2D3) are dependent on these genes. Two culture models were used, one involving 19-day fetal calvariae, to evaluate the direct resorptive activity of osteoclasis, and the other involving 45Ca-labeled 17-day fetal metatarsals, in which this activity depends on preliminary (pre)osteoclast migration. PTH similarly increased (about 10-fold) PA activity in calvariae from wild-type tPA+/+ and uPA+/+ or deficient uPA-/- and PAI-/- mice; it affected only tPA, not uPA. In tPA-/- bones, the low PA levels, due to uPA, were not influenced by PTH. Calcitonin did not affect PA responses to PTH. No differences were observed between tPA+/+, tPA-/-, uPA+/+, and uPA-/- calvariae for any parameter related to bone resorption (development of lacunae, release of calcium and lysosomal enzymes, accumulation of collagenase, loss of hydroxyproline), indicating similar responses to PTH or calcitonin. The progressive 45Ca release was largely similar in cultures of tPA+/+, tPA-/-, uPA+/+, uPA-/-, PAI+/+, or PAI-/- metatarsals and it was similarly enhanced by PTH or 1,25(OH)2D3. However, uPA-/- metatarsals released 45Ca at a slower rate at the beginning of the cultures, suggesting an impaired recruitment of the (pre)osteoclasts, which migrate at that time from the periosteum into the calcified cartilage. Thus, it appears that the direct resorptive activity of the osteoclasts does not necessitate the presence of either tPA or uPA, but uPA is likely to facilitate the migration of the (pre)osteoclasts toward the mineralized surfaces. Although considerably enhanced by PTH, tPA does not mediate the actions of PTH (nor of 1,25[OH]2D3) evaluated in these models.

    背景与目标: 纤溶酶原激活剂(PA)参与细胞迁移和组织重塑,这是骨吸收过程的两个组成部分。我们使用具有灭活的组织PA(tPA),尿激酶PA(uPA)或1型PA抑制剂(PAI-1)基因的小鼠,评估了这些过程,还是甲状旁腺激素(PTH)或1,25-二羟基维生素( 1,25 [OH] 2D3)依赖于这些基因。使用了两种培养模型,一种涉及19天胎儿颅盖骨,以评估骨吸收的直接吸收活性,另一种涉及45Ca标记的17天胎儿meta骨,其中该活性取决于破骨细胞的前期迁移。在野生型tPA /和uPA /或缺乏的uPA-/-和PAI-/-小鼠的颅脑中,PTH相似地增加了PA活性(约10倍);它仅影响tPA,而不影响uPA。在tPA-/-骨骼中,由于uPA而导致的低PA水平不受PTH的影响。降钙素不影响PA对PTH的反应。对于与骨吸收有关的任何参数(腔隙的发展,钙和溶酶体酶的释放,胶原酶的积累,羟脯氨酸的损失),tPA /,tPA-/-,uPA /和uPA-/-颅盖骨之间未观察到差异,表明对PTH或降钙素的反应相似。在tPA /,tPA-/-,uPA /,uPA-/-,PAI /或PAI-/-tar骨的培养物中45Ca的逐步释放在很大程度上相似,并且通过PTH或1,25(OH)2D3得以类似地增强。但是,uPA-/-meta骨在培养开始时以较慢的速率释放45Ca,这表明破骨细胞的吸收减弱,破骨细胞在那时从骨膜迁移到钙化的软骨中。因此,似乎破骨细胞的直接吸收活性并不需要存在tPA或uPA,但是uPA可能促进破骨细胞向矿化表面的迁移。尽管PTH大大增强了它的作用,但tPA并未介导在这些模型中评估的PTH的作用(也不超过1,25 [OH] 2D3)。

  • 【饮食中钙的补充和激素替代疗法对骨转换和钙营养激素的血清水平的不同作用。】 复制标题 收藏 收藏
    DOI:10.1007/BF01626539 复制DOI
    作者列表:Aloia JF,Vaswani A,Yeh JK,Russo L
    BACKGROUND & AIMS: :The mechanism of action of retardation of postmenopausal bone loss may be different for dietary calcium augmentation and hormonal replacement therapy (HRT). We performed a three-arm, placebo-controlled, randomized clinical trial comparing an intake of calcium of 1700 mg with: (1) calcium augmentation with HRT and (2) placebo. One hundred and eighteen women entered the study; 17 patients dropped out of the study. The vast majority of women were less than 2 years postmenopause. Bone mineral density declined significantly in the placebo group. The previously reported rates of change in the HRT group were significantly positive for total body calcium and the trochanter and not significantly different from zero for the others. The rate of change in the calcium augmentation group was intermediate between that in the two other groups, and achieved statistical significance compared with placebo for the total body calcium measurement and for the neck of the femur. Measurements were made prior to treatment and at the end of the study (2.9 years +/- 1.1 SD) for parameters of bone turnover and the calcitrophic hormones, to examine whether the mechanism of action was different for calcium augmentation versus hormonal therapy. There were no changes in the placebo group. The calcium augmentation group had a significant increase in 24-h urinary calcium and declining values for urinary collagen cross-links (pyridinium and deoxypyridinium), urinary hydroxyproline and calcitriol. The group treated with HRT and dietary calcium augmentation also had an increase in urinary calcium and a decline in collagen cross-links and urinary hydroxyproline and skeletal alkaline phosphatase; serum calcitriol did not change. The HRT group also displayed a drop in serum osteocalcin, and an increase in nephrogenous cAMP. Serum parathyroid hormone remained unchanged in all groups. Dietary calcium augmentation retards postmenopausal bone loss by decreasing resorption. The addition of HRT results in a more marked decline in bone resorption parameters and a suppression of parameters of bone formation. Whereas calcium augmentation suppressed calcitriol levels, the addition of HRT resulted in maintenance of calcitriol levels, possibly through enhancement of the renal effects of parathyroid hormone, although other mechanisms are possible.
    背景与目标: :对于饮食中的钙增加和激素替代疗法(HRT),绝经后骨质流失延迟的作用机理可能有所不同。我们进行了一项三臂,安慰剂对照的随机临床试验,比较了1700 mg钙的摄入量与:(1)HRT补钙和(2)安慰剂。一百一十八名妇女进入研究。 17名患者退出研究。绝大部分女性在绝经后不到2年。安慰剂组的骨矿物质密度显着下降。先前报道的HRT组变化率对人体总钙和转子显着为阳性,而对其他人则无显着差异。钙增加组的变化率介于其他两组之间,并且与安慰剂相比在全身钙测量和股骨颈方面具有统计学意义。在治疗前和研究结束时(2.9年/-1.1 SD)进行骨代谢和钙营养激素参数的测量,以检查钙增加与激素治疗的作用机制是否不同。安慰剂组没有变化。补钙组的24小时尿钙显着增加,尿胶原交联键(吡啶和脱氧吡啶鎓),尿羟脯氨酸和骨化三醇的值下降。接受HRT和饮食补钙的组尿钙增加,胶原蛋白交联和尿羟脯氨酸和骨骼碱性磷酸酶下降。血清骨化三醇没有改变。 HRT组还显示血清骨钙素下降,而肾源性cAMP升高。血清甲状旁腺激素在所有组中均保持不变。饮食中钙的增加通过减少吸收来延缓绝经后的骨质流失。 HRT的添加导致骨吸收参数的下降更为明显,并且抑制了骨形成参数。尽管钙的增加抑制了骨化三醇的水平,但加入HRT可能通过维持甲状旁腺激素的肾脏作用增强了骨化三醇的水平,尽管其他机制也是可能的。
  • 【在患有45,X / 46,XY性腺发育不全的患者中,双侧性腺母细胞瘤产生类固醇激素。】 复制标题 收藏 收藏
    DOI:10.1159/000293266 复制DOI
    作者列表:Fukamatsu Y,Tsukahara Y,Hayashi S,Yoshikawa F,Fukuta T
    BACKGROUND & AIMS: :A case of bilateral gonadoblastoma in a phenotypic female with 45,X/46,XY gonadal dysgenesis is presented. Hormonal investigations revealed that serum testosterone, estradiol and beta-human chorionic gonadotropin decreased following excision of the tumors, but follicle-stimulating hormone and luteinizing homrone levels increased further. Immunohistochemical staining for testosterone and estradiol was positive in both Leydig and lutein-like cells in the tumor. It is suggested that gonadoblastoma is capable of producing testosterone and estradiol, and Leydig or lutein-like cells may be the actual source of these steroid hormones.
    背景与目标: :一例表型为女性的双侧性成角细胞瘤患者患有45,X / 46,XY性腺发育不全。激素研究表明,切除肿瘤后,血清睾丸激素,雌二醇和β-人绒毛膜促性腺激素下降,但促卵泡激素和促黄体生成的激素含量进一步增加。肿瘤的睾丸间质和叶黄素样细胞中睾丸激素和雌二醇的免疫组织化学染色均为阳性。有研究表明,性腺母细胞瘤能够产生睾丸激素和雌二醇,Leydig或叶黄素样细胞可能是这些类固醇激素的实际来源。
  • 【淡季男女运动员中的内源性合成代谢和分解代谢类固醇激素。】 复制标题 收藏 收藏
    DOI:10.1055/s-2007-1024771 复制DOI
    作者列表:Tegelman R,Johansson C,Hemmingsson P,Eklöf R,Carlström K,Pousette A
    BACKGROUND & AIMS: :Peripheral serum hormone levels during the off season were analysed in 10 male and 10 female athletes, all belonging to the Swedish national teams in skiing and orienteering and in age matched sedentary controls (15 males, 13 females). No clinical signs of overuse strain were observed in any of the athletes. No significant differences in hormone variables were found between male athletes and controls. The female athletes had significantly higher levels of cortisol and significantly lower ratios between total testosterone and cortisol, between non-SHBG-bound testosterone and cortisol and between 4-androstene-3, 17-dione and cortisol than the sedentary controls. The increased levels of cortisol found in the female athletes probably reflect an adaptation to several years of hard training. A decrease of the free T/cortisol ratio has earlier been shown to indicate an overuse distress. One may speculate that the low androgen/cortisol ratios found in the female athletes in contrast to the males could indicate that the female athletes might need longer time to recover from hard exercise than male athletes, or could suggest an insufficient dietary intake.
    背景与目标: :分析了淡季期间10名男性和10名女性运动员的血清血清激素水平,这些运动员全部属于瑞典国家队的滑雪和定向越野及与年龄相匹配的久坐控制(15名男性,13名女性)。在任何运动员中均未观察到过度劳损的临床征象。在男性运动员和对照组之间,激素变量没有发现显着差异。与久坐的对照组相比,女运动员的皮质醇水平显着较高,而总睾丸激素和皮质醇之间,未与SHBG结合的睾丸激素和皮质醇之间,以及4-雄甾烯-3、17-二酮和皮质醇之间的比率显着较低。在女运动员中发现的皮质醇水平升高,可能反映了对数年艰苦训练的适应。游离T /皮质醇比值的降低早已显示出过度使用的困扰。可以推测,与男性相反,女性运动员中雄激素/皮质醇的比率较低,这可能表明女性运动员比男性运动员可能需要更长的时间才能从剧烈运动中恢复过来,或者表明饮食摄入不足。
  • 【类固醇激素与神经系统之间的相互作用。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Spindler KD
    BACKGROUND & AIMS: After a short description of the endocrine and nervous system and their similarities and differences, interactions between both parts are mainly dealt with in this brief review. This is especially exemplified by the modulation of receptors for neurotransmitters, of ion channels and other membrane components by neurosteroids and steroid hormones and the physiological significance of this regulation. Both classes of hormones can act via nongenomic and genomic actions. As biological responses to neurosteroids and steroid hormones in the nervous system exocytosis of peptide hormones and neurosteroids, regulation of neurotransmitter release, sexual brain development and male behavior and cell death are described. Neurotransmitters and their receptors are also modulated in their expression and biological activity by steroid hormones and neurosteroids in non-neuronal tissues, as demonstrated for GABA-receptors in the uterus and the embryonic cholinergic system. Because of the close links between endocrine and nervous system agents toxic for one component may also interfere with the other one.

    背景与目标: 在简短描述内分泌和神经系统及其异同之后,本文将主要讨论这两个部分之间的相互作用。神经类固醇和类固醇激素对神经递质的受体,离子通道和其他膜成分的调节及其调节的生理意义,尤其可以说明这一点。这两类激素均可通过非基因组和基因组作用起作用。作为神经系统对肽激素和神经甾体的胞吐作用的神经甾体和甾体激素的生物学反应,描述了神经递质释放的调节,性脑发育以及男性行为和细胞死亡。神经递质及其受体的表达和生物活性也受到非神经元组织中类固醇激素和神经甾体的调节,如子宫和胚胎胆碱能系统中的GABA受体所证明的。由于内分泌和神经系统物质之间的紧密联系,对一种成分有毒的物质也可能干扰另一种物质。

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