BACKGROUND & AIMS: :We investigated how visitor-use affects water quality in wilderness in Yosemite National Park. During the summers of 2012-2014, we collected and analyzed surface-water samples for water-quality indicators, including fecal indicator bacteria Escherichia coli, nutrients (nitrogen, phosphorus, carbon), suspended sediment concentration, pharmaceuticals, and hormones. Samples were collected upstream and downstream from different types of visitor use at weekly to biweekly intervals and during summer storms. We conducted a park-wide synoptic sampling campaign during summer 2014, and sampled upstream and downstream from meadows to evaluate the mitigating effect of meadows on water quality. At pack stock stream crossings, Escherichia coli concentrations were greater downstream from crossings than upstream (median downstream increase in Escherichia coli of three colony forming units 100 mL-1), with the greatest increases occurring during storms (median downstream increase in Escherichia coli of 32 CFU 100 mL-1). At backpacker use sites, hormones, and pharmaceuticals (e.g., insect repellent) were detected at downstream sites, and Escherichia coli concentrations were greater at downstream sites (median downstream increase in Escherichia coli of 1 CFU 100 mL-1). Differences in water quality downstream vs. upstream from meadows grazed by pack stock were not detectable for most water-quality indicators, however, Escherichia coli concentrations decreased downstream, suggesting entrapment and die-off of fecal indicator bacteria in meadows. Our results indicate that under current-use levels pack stock trail use and backpacker use are associated with detectable, but relatively minor, effects on water quality, which are most pronounced during storms.

背景与目标： : 我们调查了游客的使用如何影响优胜美地国家公园荒野中的水质。在2012-2014年夏季，我们收集并分析了地表水样品的水质指标，包括粪便指示细菌大肠杆菌，营养物质 (氮，磷，碳)，悬浮沉积物浓度，药物和激素。在每周至每两周的间隔以及夏季风暴期间，从不同类型的访客使用的上游和下游收集样本。我们在夏季2014进行了公园范围的天气采样活动，并从草甸的上游和下游采样，以评估草甸对水质的缓解作用。在pack种群流过境处，从过境处下游的大肠杆菌浓度高于上游 (三个菌落形成单位100   mL-1的大肠杆菌的下游中位值增加)，其中最大的增加发生在风暴期间 (大肠杆菌的下游中位值增加32 CFU 100   mL-1)。在背包客使用地点，在下游地点检测到激素和药物 (例如，驱虫剂)，并且在下游地点检测到大肠杆菌浓度更高 (大肠杆菌的下游增加中位数为1 CFU 100 mL-1)。对于大多数水质指标，无法检测到填鸭式草甸下游与上游的水质差异，但是，下游的大肠杆菌浓度降低，表明草甸中粪便指示细菌的截留和死亡。我们的结果表明，在当前使用水平下，包装库存的使用和背包客的使用与可检测但相对较小的水质影响有关，这在暴风雨期间最为明显。

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： : 不仅在孤立的细胞核中，而且在所有主要的核外细胞成分中都存在具有相似特征的甲状腺激素的 “高亲和力饱和” 结合位点，以及细胞质不能促进核结合，使与类固醇激素受体的类比无效，并且需要对当前与体外核制剂中甲状腺激素结合的方法的生理相关性进行更严格的评估。

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interleukin-6 (IL-6) 和各种水平的脂肪因子 (瘦素和脂联素)，而ghrelin抵消了瘦素在癌症引起的厌食-恶病菌综合征中的厌食作用。我们旨在了解IL-6，脂肪因子和ghrelin血浆水平如何一方面受到癌症的影响，另一方面又受到老年癌症患者的年龄，虚弱和营养状况的影响。包括99名79岁 [76-83] 岁的患者。60 6% 人患有晚期癌症，34% 人患有恶病菌。50% 的人有营养不良的风险，10% 有明显的营养不良。研究的变量均未与晚期或恶食症显着相关。在多元回归中，与年龄显著正相关的唯一参数是脂联素 (p = 0.008)。尽管我们的研究中脆弱的患病率很高，但在多变量分析中，我们没有发现脆弱 (通过G8评估) 与IL-6，瘦素，脂联素或ghrelin有任何独立关联。我们观察到低白蛋白水平与较高水平的IL-6独立相关 (p <0.0001)，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的持久性，即使在老年癌症患者中也是如此。最后，高IL-6水平与较高的死亡率相关 (p = 0.027)。总之，在老年癌症患者中，IL-6，瘦素，脂联素和ghrelin与癌症的晚期或癌症诱发的恶病菌无关，但它们与人体测量因素和身体组成显着相关。

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： : 来自大麻哈鱼的黑色素刺激激素 (MSHs) 导致色素分散在medaka (一种硬骨鱼) 的分离黑色素中。体外的medaka黑色素团生物测定法可对色素分散液的光和对色素聚集的黑暗产生反应，用于测量促黑素激素的活性。alpha-MSH I是测试的最有效的黑色素分散剂。诱导色素分散的最小剂量分别为10(-15) M α-MSH I、10(-13) M N-去乙酰基 (Ac)-α-MSH和10(-11) M β-MSH I。鲑鱼N-乙酰内啡肽I (N-Ac-EP) 增强了 β-MSH I的黑素体分散活性约40%。结果表明，n-ac-ep可能是某些MSHs活性的增强剂。本生物测定法提供了一种用于确定促黑肽的生物活性的独特方法。

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： : 代谢过程受体温和甲状腺激素的影响。温度是卵生脊椎动物孵化长度的主要决定因素，但海龟也可以独立于温度改变发育速率。自然巢内的温度梯度会导致巢内海龟胚胎的发育速率不同。尽管温度引起的发育速率降低，但低温孵育的新生儿通常通过代谢补偿与温暖的兄弟姐妹同步孵化。代谢补偿的生理机制尚不清楚，但甲状腺激素可能起着关键作用。我们将过量的三碘甲腺原氨酸 (T3) 应用于默里河短颈龟 (Emydura macquarii) 的发育卵 (一种具有代谢补偿和同步孵化的物种)，以确定T3是否影响发育速率以及潜伏期的变化是否会产生代谢成本。我们测量了心率，耗氧量和卵的潜伏期，以及幼体的形态和性能。尽管总代谢消耗没有变化，并且孵化形态也没有处理差异，但暴露于T3的胚胎比未处理的对照早3.5 d。用T3处理的幼体表现出与对照组的幼体相似的扶正能力。暴露于T3会通过加速胚胎发育而缩短孵育时间，但不会在统计学上增加胚胎代谢。因此，T3是一种机制，可以用较冷的爬行动物来加速其发育，以允许与较热的离合器伴侣同步孵化，但几乎没有代谢成本。因此，如果T3是潜在的机制，则同步孵化的代谢补偿可能在代谢上并不昂贵。

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： : 这项研究的目的是研究高强度冲刺和力量训练 (HISST) 对年轻 (20岁) 和中年 (40岁) 男性的糖调节激素的影响。36名受过中等训练的男性作为志愿者参加了这项研究。体检后，符合条件的受试者根据年龄随机分为四组之一: 青年训练组 (21.3   ±   1.3岁，YT，n   =   9)，青年对照组 (21.4   ±   1.7岁，YC，n   =   9)，中年训练组 (40.7   ±   1.8岁，AT，n   =   9)，中年对照组 (40.5   ±   1.8岁，AC，n   =   9)。YT和AT参加了HISST 13周。在HISST之前和之后，所有参与者都进行了Wingate厌氧测试 (WAnT)。在休息时，预热后 (50% VO2max)，想要后立即和想要后10  min收集血样。在HISST之前，我们观察到AT (5.86   ±   0.32 mmol.L-1) 的葡萄糖浓度明显高于静止时的YT (4.24   ±   0.79 mmol.L-1)，并响应于WAnT (6.56   ±   0.63 mmol.L-1 vs. 5.33   ±   0.81 mmol.L-1)。在WAnT反应中，AT的皮质醇水平显著高于YT (p  <  0.05) (468   ±   99.50 ng ng.mL-1 vs. 382   ±   64.34 ng ng.mL-1)。在休息和WAnT反应中，儿茶酚胺水平以类似的方式上升。在HISST之后，这种 “年龄效应” 在休息和训练组 (YT和at) 的运动中消失了。剧烈训练时激素浓度的变化是由于各种组织的适应性变化，尤其是训练有素的受试者的骨骼肌和肝脏。HISST可能至少部分抵消了对葡萄糖代谢的负面 “年龄效应”。

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：

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： : 很大程度上归因于对可持续性的担忧，在水产养殖鱼类中利用富含omega-3长链多不饱和脂肪酸 (n-3 LC-PUFA) 鱼油是一个越来越令人关注的问题。因此，正在研究使这些关键健康有益脂肪酸的沉积效率最大化的策略。本研究研究了四种基于蔬菜的膳食脂质来源 (亚麻籽，橄榄，棕榈油和葵花籽油) 对n-3 lc-pufa沉积效率以及食欲调节激素，瘦素和生长素的循环血浆浓度的影响，在虹鳟鱼养殖的生长和整理阶段。在鱼的表现中发现了最小的有害影响; 但是，组织脂肪酸组成中明显出现了重大变化，这通常反映了饮食的变化。在鱼油整理阶段之后，这些修饰有所减少，但持久的效果仍然很明显。已证明替代油的脂肪酸组成对n-3 lc-pufa的沉积效率以及在生长和精加工阶段参与食欲调节，生长和饲料摄入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 “消除” 了n-3 LC-PUFA的分解代谢，因此导致这些脂肪酸的最高保留，最终强调新的营养方法，以最大程度地维持鱼油在水产养殖物种饲料中使用时的质量效益。

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： : 在449名40岁及以上的女性中，研究了随着年龄增长而血清促性腺激素和类固醇激素水平的变化，以研究这些激素之间的关系，甚至在生命的晚期。50岁后，雌二醇 (E2) 和硫酸脱氢表雄酮 (dhea-s) 的水平下降，此后保持较低水平。然而，尽管血清雌酮 (E1)，睾丸激素 (T)，delta-4-androstenedione (A) 和催乳素 (PRL) 的浓度在50岁后也最初降低，但随后又逐渐升高，并且在E1的情况下，这种增加实际上是显着的。黄体生成素 (LH) 和卵泡刺激素 (FSH) 在50岁后上升，但FSH仍然升高，LH在生命后期下降。皮质醇 (F) 在70岁后显着增加。即使在60岁以后，雄激素与E1之间以及E2与LH之间也存在显着相关性。由于所研究人群的异质性很大，因此尚无法推测这些观察的生理病理意义。然而，似乎雌激素对LH分泌的负反馈作用在生命的后期仍然有效。

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卵巢激素的内源性状态对 β-肾上腺素受体激动剂异丙肾上腺素 (异丙肾上腺素) 和多巴酚丁胺在胸主动脉段中诱导的松弛的影响，来自年龄匹配的 (13周大) 处女 (发情期) 和去卵巢 (OVX) 青春期前雌性Wistar大鼠。与发情大鼠相比，OVX大鼠完整主动脉段异丙肾上腺素诱导的松弛减少。通过内皮去除，1微mol/l普萘洛尔或100微mol/l N(G)-硝基-L-精氨酸甲酯 (l-name) 显着降低松弛。与异丙肾上腺素相比，β (1)-肾上腺素受体激动剂多巴酚丁胺在发情期大鼠的完整动脉中引起的松弛较少，而多巴酚丁胺在OVX的完整节段中引起的松弛明显较少。这种多巴酚丁胺诱导的松弛通过内皮去除消除，并被1微摩尔/升普萘洛尔、100微摩尔/升l-name或1微摩尔/升育亨宾还原。霍乱毒素 (刺激性g蛋白G(s) 的激活剂) 引起发情大鼠完整动脉的松弛; 卵巢激素的剥夺和内皮的去除均降低了这种松弛。Forskolin (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cGMP依赖性血管扩张激动剂) 在发情和OVX大鼠的动脉中诱导了类似的非内皮依赖性舒张。这些结果表明，剥夺女性卵巢激素会损害大鼠胸主动脉中内皮 β-肾上腺素受体激活引起的松弛; 这种损害至少部分是由NO和G(s) 功能的内皮释放减少引起的。

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，保护女性肾损伤的分子机制尚不清楚。这项研究的目的是确定性激素是否在男性和女性自发性高血压大鼠 (SHR) 的高血压发育期调节血压和蛋白尿的进展。还进行了研究，以检查性别和性激素如何影响蛋白尿的两个主要危险因素，肾素-血管紧张素系统的过度激活和氧化应激。通过遥测测量性腺完整和性腺切除的男性和女性SHR的血压。随时间推移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，而女性则无影响。随着时间的推移，男性SHR表现出对性腺敏感的蛋白尿增加，而女性SHR在巨噬细胞浸润中表现出对性腺敏感的抑制。与男性相比，女性SHR的血浆ANG II水平更高，肾皮质ANG II水平相似，但肾皮质中AT(1)-受体蛋白表达较少。女性SHR在肾脏氧化应激中也具有性腺敏感性降低。因此，对女性SHR提供的肾脏保护与降低血压，减少巨噬细胞浸润和降低氧化应激水平有关。

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) 与细胞迁移和组织重塑有关，这是骨吸收过程的两个组成部分。使用具有灭活组织PA (tPA)，尿激酶PA (uPA) 或1型PA抑制剂 (PAI-1) 基因的小鼠，我们评估了这些过程或甲状旁腺激素 (PTH) 或1,25-二羟基维生素 (1,25[OH]2D3) 的刺激是否依赖于这些基因。使用了两种培养模型，一种涉及19天胎儿颅骨，以评估破骨细胞的直接吸收活性，另一种涉及45ca标记的17天胎儿跖骨，其中该活性取决于破骨细胞的初步 (前) 迁移。PTH类似地增加 (约10倍) 野生型tPA +/+ 和uPA +/+ 或缺陷型uPA-/-和PAI-/-小鼠颅骨中的PA活性; 它仅影响tPA，不是uPA。在tPA-/-骨骼中，由于uPA引起的低PA水平不受PTH的影响。降钙素不影响PA对PTH的反应。tPA/，tPA-/-，uPA/，uPA-/- calvariae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)，表明对PTH或降钙素的反应相似。tPA-/-、uPA +/+ 、uPA-/-、PAI +/+ 或PAI-/-跖骨，PTH或1,25(OH)2D3也同样增强。然而，uPA-/-跖骨在培养开始时以较慢的速度释放45Ca，这表明破骨细胞的募集受损，破骨细胞当时从骨膜迁移到钙化软骨中。因此，似乎破骨细胞的直接吸收活性并不需要tPA或uPA的存在，但是uPA可能会促进 (前) 破骨细胞向矿化表面的迁移。尽管PTH显着增强，tPA不会介导PTH的作用 (也不是1，在这些模型中评估了25[OH]2D3)。

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： : 饮食钙增加和激素替代疗法 (HRT) 的绝经后骨丢失延迟的作用机制可能不同。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钙增强和 (2) 安慰剂。一百十八名妇女参加了研究; 17名患者退出了研究。绝大多数女性绝经后不到2年。安慰剂组的骨矿物质密度显着下降。先前报告的HRT组的变化率对全身钙和转子的变化显着阳性，而其他组的变化与零没有显着差异。钙增强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。在治疗之前和研究结束时 (2.9年/- 1.1 SD) 对骨转换和钙调激素的参数进行了测量，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。钙增强组24小时尿钙显着增加，尿胶原交联 (吡啶鎓和脱氧吡啶鎓)，尿羟脯氨酸和骨化三醇的值下降。接受HRT和饮食钙增加治疗的组的尿钙也增加，胶原蛋白交联，尿羟脯氨酸和骨骼碱性磷酸酶也减少。血清骨化三醇没有变化。HRT组还显示血清骨钙素下降，肾源性cAMP增加。所有组的血清甲状旁腺激素均保持不变。膳食钙增加通过减少吸收来延缓绝经后骨丢失。添加HRT会导致骨吸收参数明显下降，并抑制骨形成参数。钙的增加抑制了骨化三醇的水平，而HRT的添加可能通过增强甲状旁腺激素的肾脏作用来维持骨化三醇的水平，尽管其他机制也是可能的。

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： : 一例表型女性双侧性腺母细胞瘤，45，X/46，XY性腺发育不全。激素研究表明，肿瘤切除后血清睾丸激素，雌二醇和 β-人绒毛膜促性腺激素降低，但促卵泡激素和黄体生成素水平进一步升高。在肿瘤的Leydig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。建议性腺母细胞瘤能够产生睾丸激素和雌二醇，而Leydig或叶黄素样细胞可能是这些类固醇激素的实际来源。

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名女性运动员的外周血清激素水平，这些运动员均属于瑞典国家队的滑雪和定向越野运动以及年龄匹配的久坐对照组 (15名男性，13名女性)。在任何运动员中均未观察到过度使用应变的临床迹象。男性运动员和对照组之间的激素变量没有显着差异。与久坐的对照组相比，女运动员的皮质醇水平明显更高，总睾丸激素和皮质醇之间，非SHBG结合的睾丸激素和皮质醇之间以及4-雄烯酮-3,17-二酮和皮质醇之间的比率明显更低。在女运动员中发现的皮质醇水平升高可能反映了对几年艰苦训练的适应。较早前已显示游离T/皮质醇比率的降低表明过度使用困扰。人们可能会推测，与男性相比，女性运动员的雄激素/皮质醇比率较低，这可能表明女性运动员可能比男性运动员需要更长的时间才能从艰苦的运动中恢复，或者可能表明饮食摄入不足。