肿瘤坏死因子及前列腺素对卵巢颗粒细胞增殖及雌、孕激素分泌的影响

应用来自体外授精(IVF)或配子移植(GIFT)患者的卵巢颗粒黄体细胞(GL细胞),纯化后培养10日,观察在肿瘤坏死因子α(TNF_α)作用下,对细胞增殖及雌、孕激素分泌的影响。加入重组人TNF_α0.1～10ng/ml后,GL细胞增殖加快,以第0～2日最显著,TNF_α10ng组较对照组增殖一倍。在培养第4～10日TNF10ng组孕激素(P_4)和雌激素(E_2)分泌量增加。若按细胞计每细胞P_4分泌量并无增加而E_2在第8～10日分泌量增加,在培养的GL细胞中加入前列腺素E_2(PGE_2)时,显示PGE_2抑制TNF使GL细胞增殖的作用。提示TNF可促进GL细胞增殖及P_4、E_2分泌增加,并对黄体形成起一定作用。     

雌、孕激素对卵巢切除小鼠子宫骨桥蛋白表达的影响

目的探讨雌激素和孕激素对卵巢切除小鼠子宫骨桥蛋白（osteopontin,OPN）表达的影响。方法将性成熟雌性昆明小鼠切除卵巢后分为注射芝麻油（对照组）、17β-雌二醇（E组）25ng／只,孕酮（P组）2mg／只,E25ng＋P2mg／只（E＋P组）,给药3d后取小鼠子宫;另设单次注射17β-雌二醇25ng／只（E组）及芝麻油（对照组）后6、12和24h取子宫进行比较。采用免疫组织化学及逆转录-聚合酶链式反应（RT—PCR）法检测小鼠子宫骨桥蛋白的定位及mRNA的转录。结果（1）OPN的免疫染色主要位于子宫内膜腔上皮、腺上皮和间质。对照组均未检测到OPN。E组OPN的免疫染色最强,E＋P组次之,P组最弱。在雌激素作用不同时间,6h在腺上皮OPN的免疫染色弱阳性,12h腺上皮、腔上皮OPN的免疫染色阳性,24h腔上皮、腺上皮和间质均可见较强的OPN免疫染色。（2）E组OPN的mRNA转录水平显著增高,且与E＋P组、P组和对照组相比均有显著性差异（P〈0．05）;E＋P组、P组也可促进OPN的mRNA转录,但与对照组相比差异均无显著性（P〉0．05）。在雌激素作用不同时间,6h、12h和24h组均可检测到OPN的mRNA转录,与对照组比较均有显著性差异（分别为P〈0．05,P〈0．05和P〈0．01）;24h组OPN的mRNA转录显著增高,与6h组和12h组比较均有显著性差异（P〈0．01）,6h组与12h组比较差异无显著性（P〉0．05）。结论小鼠子宫内膜的OPN最初是由腺上皮分泌的,雌激素可诱导小鼠子宫内膜OPN的表达,孕激素的作用不明显。     

外源性雌激素对卵巢切除小鼠骨折愈合影响的组织学观察

目的　探讨外源性雌激素对骨折愈合的影响。方法　在卵巢切除后 3个月已经出现明显骨丢失的balb/c小鼠用折骨器造成右股骨中段闭合性骨折 ,应用不同剂量的雌激素治疗 ,然后分批处理取出骨痂标本进行组织学检查。结果　发现卵巢切除后未用雌激素治疗小鼠骨痂形成较小 ,而应用高剂量雌激素治疗小鼠骨痂发育明显推迟。结论　实验表明 ,补充超生理剂量雌激素对卵巢切除小鼠骨折愈合 (早期 )不利。     

闭经患者雌激素与雄激素对骨密度的影响

为了解原发闭经和继发闭经患者的雌雄激素水平与骨密度的关系,收集了１８～５１岁原发闭经患者９０例,继发闭经患者２６０例,并以相同年龄正常月经１８０例为对照组。分别测定其血清雌二醇和睾酮水平,测量皮质骨和松质骨骨密度。结果：原发闭经和继发闭经患者的雌激素均低于正常对照组。２１－羟化酶缺乏患者的雌激素水平稍低但雄激素远高于其它各类闭经患者和正常对照组。各类原发闭经和继发闭经患者的皮质骨和松质骨骨密度均低于同年龄正常对照组,唯独２１－羟化酶缺乏患者骨密度不但未降低反而升高３．１％。多囊性卵巢综合征患者的骨密度降低较少,它与２１－羟化酶缺乏二者均有高雄激素的临床特征。总之,原发闭经患者骨密度低于继发闭经患者,松质骨的骨密度较皮质骨更低。结果表明雌激素和雄激素缺乏均可影响骨密度,雌、雄激素缺乏越早,骨密度越低     

功能试验用于鉴别多囊卵巢综合征患者过多雄激素的来源

为探索简便易行、适用于临床鉴别多囊卵巢综合征（ＰＣＯＳ）过多雄激素来源的方法，对１１例雄激素增高的ＰＣＯＳ患者进行雄烯二酮（Ａ２）与皮质醇（Ｆ）的同步释放试验、地塞米松抑制试验及舒经酚刺激试验，随后进行舒经酚诱导排卵治疗，对舒经酚耐药者辅以地塞米松治疗。结果：（１）４例Ａ２与Ｆ的同步变化不明显，地塞米松对Ａ２的抑制也不明显，舒经酚刺激后Ａ２及雌二醇（Ｅ２）升高明显，舒经酚诱导排卵７个周期中５个周期排卵，提示过多雄激素主要来源于卵巢。（２）７例Ａ２与Ｆ的同步变化明显，地塞米松对Ａ２明显抑制，舒经酚刺激后Ａ２及Ｅ２升高不明显，舒经酚诱导排卵１３个周期中仅２个周期排卵。辅以地塞米松治疗后，２例排卵并获妊娠，表明过多雄激素除卵巢外，兼有肾上腺来源。提示综合舒经酚刺激试验与地塞米松抑制试验，以Ａ２及Ｅ２为指标，可用于鉴别ＰＣＯＳ患者过多雄激素的不同来源，同步释放试验对鉴别也有一定意义，雄激素基础水平的测定对鉴别意义不大。     

雄激素、雌激素与男性骨质疏松症

近年研究发现男性骨质疏松症与体内雄激素和雌激素水平呈正相关.雄激素通过刺激成骨细胞增殖和发育来促进骨骼生长,对维持骨量和提高骨密度起重要作用.雌激素对骨的作用可能是降低骨吸收而非促进骨形成,通过与成骨细胞上的受体结合而间接调控成骨细胞功能.但有研究认为睾酮对雄激素受体的亲和力和活性相对较低.睾酮在5α还原酶作用下代谢为双氢睾酮,进而代谢为雌二醇,或在芳香化酶作用下直接转变为雌激素,与雌激素受体结合而发挥生理学作用.该文就雄激素和雌激在男性骨质疏松症中的作用机制及激素替代疗法临床应用进展作一综述.     

氟化物及氟化物加钙对卵巢切除大鼠血清中LPO变化的影响

目的 确定氟化物及钙对卵巢切除大鼠血清脂质过氧化物的影响。方法 64只雄性Wistar大鼠,随机分为卵巢切除组,卵巢切除后单纯喂给氟组及卵巢切除后喂给氟加钙组。喂养6个月后,处死动物,测定血中的脂质过氧化物含量。结果 卵巢切除组血中OPO含量明显高于对照组（P＜0．05）。卵巢切除同时喂给不同剂量的氟及氟加钙组,大鼠血清OPO明显低于单纯卵巢切除组（P＜0．01）。卵巢切除同时投给不同剂量的氟与卵巢切除同时投给不同剂量的氟加钙组比较大鼠血清LPO改变不明显（P＞0．05）。结论 卵巢切除骨质疏松大鼠血中LPO明显增高,加入不同剂量的氟及钙后改善了去势大鼠的脂质过氧化程度。     

多囊卵巢综合征患者血雄激素与胰岛素、黄体生成素水平关系的探讨

血高雄激素是多囊卵巢综合征 (PCOS)的主要生化特征。以往认为高黄体生成素 (LH)是PCOS高雄激素的主要因素 ,现在证明高胰岛素 (INS)与高雄激素关系密切。为了进一步探讨高INS、高LH与高雄激素的关系 ,我们对PCOS患者的血激素水平进行了比较分析。一、材料与方法1 病例选择 :1 998年 3月至 2 0 0 2年 3月在本院妇科内分泌门诊就诊的PCOS患者 1 1 8例 ,入组条件 :(1 )B超监测每侧卵巢有 >1 0个的卵泡直径 2～8mm ,卵巢基质密度增强 ;(2 )月经稀发 ;(3)睾酮 (T)>2 .2nmol/L和 (或 )雄稀二酮 (A) >9nmol/L或黄体生成素 /卵泡刺激…     

雌激素对卵巢切除大鼠内源性白细胞介素-6变化的影响

目的：探讨卵巢切除后大鼠内源性白细胞介素－６（ＩＬ－６）的变化及雌激素替补治疗对此的影响。方法：通过酶联免疫吸收法检测骨髓上清的ＩＬ－６含量,通过斑点杂交和免疫组织化学方法检测骨组织ＩＬ－６的表达和分布。结果：卵巢切除导致骨髓上清ＩＬ－６含量细胞均有较强的ＩＬ－６免疫活性。结论：雌激素缺乏使骨髓内源性ＩＬ－６增加可能是由于骨细胞系ＩＬ－６ｍＲＮＡ表害升高决定的,雌激素抗骨吸收作用部分是通过降低ＩＬ     

The effect of warfarin on urine calcium oxalate crystal growth inhibition and urinary excretion of calcium and nephrocalcin

Summary Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The presence of Gla may be important to its ability to inhibit crystal growth. Several studies suggest that vitamin K-dependent proteins may also play a role in renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men while they were taking warfarin for a mean of 252 days, and again a mean of 64 days after its discontinuation. Urinary Ca excretion did not differ between those on or off warfarin, or between those on warfarin and normal controls. The ability of the subjects' urine to inhibit CaOx crystal growth did not differ on or off warfarin, or from that of control urine, and the excretion of immunoreactive NC also did not differ between these groups. NC was found to be responsible for approximately 16% of the CaOx growth inhibition seen. These results do not suggest that vitamin K-dependent proteins play a major role in renal Ca excretion in men, or that interference with vitamin K alters NC excretion or inhibitory activity of the urine.     

外源性雌激素及三苯氧胺对大鼠乳腺癌癌前期病变的作用

目的　建立乳腺癌癌前期病变动物模型,探索外源性雌激素（EE）及其拮抗剂的作用。　方法　Wistar雌性大鼠50只,对照组12只;其余大鼠经胃管灌注7,12-二甲基苯并蒽（DMBA）,8只用正常饮料(DMBA组);15只饲料中加乙烯雌酚(DMBA＋DES组);15只饲料加三苯氧胺(DMBA＋TAM组)。3个月后检测乳腺增生、核仁形成区嗜银蛋白（AgNOR）和DNA含量。　结果　DMBA组和DMBA＋DES组的乳腺组织增生率分别为75％及93.33%;AgNOR计数为3.71±0.76及5.60±0.42;DNA含量为88.59±7.17及137.75±3.13,DMBA组及DMBA＋DES组与对照组和DMBA＋TAM组比较差异有显著意义（P＜0.01）。　结论　一次性灌注DMBA可以建立乳腺癌癌前期病变动物模型;EE可加重DMBA诱导的乳腺癌癌前期病变;而TAM则具有阻断作用。     

The effect of scoliosis surgery on parathormone,calcitonin and calcium levels in serum and the urinary excretion of calcium

Summary This study investigates mineral metabolism following scoliosis surgery in girls. During the first week there was a significant increase in the secretion of parathormone and a decrease in that of calcitonin. The serum calcium became significantly elevated from between the 3rd and 7th post-operative days. The serum phosphate decreased during the first week and increased significantly thereafter. The urinary excretion of calcium increased five-fold.

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Résumé Cet article étudie les modifications du métabolisme minéral dans les suites d'opérations pour scolioses chez des jeunes filles. Durant la première semaine, on observe une augmentation importante de la secrétion de parathormone et une diminution de la calcitonine. Par rapport à son taux initial, le calcium sérique s'élève de façon notable entre le troisième et le septième jour post-opératoire. Le phosphate sérique décroit durant la première semaine et s'accroit ensuite de façon importante. L'excrétion de calcium augmente jusqu'à quintupler.

     

雄激素对卵泡发育影响的双重性

卵泡生长发育受到内分泌、旁分泌和自分泌等因素的严格调控,其中雄激素在卵泡的募集和发育中起重要作用.但是雄激素对卵泡发育的影响犹如一把双刃剑,其作用是双重的.低剂量的雄激素可以促进卵泡的启动募集使得更多卵泡从储备池进入生长发育池,并作用于窦前卵泡和小窦卵泡上的雄激素受体促进卵泡膜间质细胞和颗粒细胞增生,减少卵泡的凋亡和闭锁.如果雄激素水平过高则会起相反的作用,在一些高雄激素疾病如多囊卵巢综合征中,过高的雄激素会抑制卵泡的选择性生长,诱导卵泡发生凋亡和闭锁,最终导致排卵功能障碍.     

The effect of crystalline monosodium urate on the crystallisation of calcium oxalate in whole human urine

Summary (1) Samples of undiluted urine from normal men were preincubated with crystalline monosodium urate and their metastable limits and responses to a standard oxalate challenge were compared with results obtained from control samples preincubated without urate. (2) Preincubation with urate had no significant effect on the metastable limits of the urines, the morphology, size, or growth rates of calcium oxalate crystals precipitated from the urines, or on the total amount of calcium oxalate deposited in a given time. (3) It was concluded that particulate monosodium urate is unlikely to influence calcium oxalate stone formation by binding to and attenuating the potency of urinary inhibitors.     

Comparative effects of oral aromatic and branched-chain amino acids on urine calcium excretion in humans

Summary In 30 adults, increasing intake of aromatic amino acids increased calcium excretion and serum IGF-1, but not indices of bone turnover, when compared with similar increases in intake of branched-chain amino acids. The mechanisms involved are not certain but these findings suggest a role for the calcium sensor receptor. Introduction In contrast to branched-chain amino acids (BCAAs), aromatic amino acids (AAAs) bind to the calcium sensing receptor (CaR) and thus have an increased potential to affect calcium homeostasis. In this study we compare the effects of increased intake of AAAs versus BCAAs on calcium excretion, serum IGF-1, markers of bone turnover, and 4-hr calcium excretion after an oral calcium load. Methods After two weeks on low-protein metabolic diets, 30 healthy subjects were randomized to a fivefold increase in intake of AAAs or BCAAs for two weeks. Changes in calcium excretion and other measures were compared in the two groups. Results With the increase in amino acid intake, 24-hr calcium excretion (P = 0.027), IGF-1 (P = 0.022), and 4-hr calcium excretion after an oral load (P = 0.023) increased significantly in the AAA relative to the BCAA group. Group changes in turnover markers did not differ significantly. Conclusion In comparison with BCAAs, AAAs promoted calcium excretion. The calciuria does not appear to result from increases in bone resorption and may occur by increasing calcium absorption. The AAAs also increased circulating levels of IGF-1. Collectively these findings raise the possibility that AAAs may selectively influence calcium homeostasis through their interactions with the CaR. Presented at the American Society of Bone and Mineral Research meeting in Nashville, Tenn., September 2005. This material is based on work supported by a Discovery Grant from Dairy Management, Inc. and by the U.S. Department of Agriculture under agreement No. 59-1950-9001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the U.S. Department of Agriculture.     

The dual effect of urinary macromolecules on the crystallization of calcium oxalate endogenous in urine

Summary The nucleation-promoting and growth-inhibiting activities of urinary macromolecules on the crystallization of calcium oxalate endogenous in urine of stoneformers and normal controls were studied by freezing the ultrafiltrate and retentate fractions of concentrated whole urine (pH 5.3, 1,250 mosmol/kg). Among the normal controls, macromolecules nominally of 10–20 kDa showed nucleation-promoting and growth-inhibiting activities; the 5–10 kDa population was incapable of such effects but did cooperate with molecules >10 kDa in enhancing the effect. In the case of stone-formers, molecules in the nominal ranges of 5–10 kDa and 10–20 kDa when considered separately were not active in the aspects studied but collectively could cooperate to produce pronounced effects. Application of the test to urine ultrafiltrate reconstituted with polyanionic macromolecules recovered from urine indicated that molecules from stoneformers were more powerful than those from normal controls in bringing about promotion of nucleation and inhibition of growth of crystals from urinary calcium oxalate.     

Effects of estradiol and dihydrotestosterone on osteoblast gene expression in osteopenic ovariectomized rats

Because androgens increase bone formation and estrogens inhibit bone resorption, there is a potential therapeutic use for a combined treatment of these hormones to preserve bone. We investigated the effect of dihy-drotestosterone (DHT) and estradiol, alone and in combination, on the mRNA levels of genes expressed during osteoblast development in osteopenic ovariectomized (ovx) rats: 40 animals were ovx and administered vehicle or 80mg/kg body weight DHT at 15 weeks postovariectomy. At 19 weeks postovariectomy, the rats were administered vehicle or 20mg/kg body weight estradiol for 1 week. The treatment groups were as follows: (1) vehicle + vehicle, (2) DHT + vehicle, (3) vehicle + estradiol, and (4) DHT + estradiol. Fasting blood and urine samples were collected at 15, 17, 19, and 20 weeks postovariectomy for bone biochemical analyses. On completion of both procedures, the long bones were removed and total RNA extracted. Combined DHT and estradiol treatment increased the mRNA (P < 0.001) and serum levels of alkaline phosphatase (ALP) (P < 0.01) compared to control rats. These data suggest that combined DHT and estradiol treatment stimulates osteoblasts at an early stage of their development when ALP is expressed.     

The effect of calcium on calcium oxalate monohydrate crystal-induced renal epithelial injury

Since hypercalciuria is a common feature of idiopathic calcium oxalate (CaOx) nephrolithiasis, renal epithelial cells of stone patients are exposed to various crystals in the presence of high calcium. This study was performed to determine the effect of high calcium levels on CaOx crystal-induced cell injury. We exposed human renal epithelial cell line, HK2 in vitro to CaOx monohydrate crystals at a concentration of 133 μg/cm² for 1, 3, 6 or 12 h in the presence or absence of 5 or 10 mM/L calcium Ca⁺⁺. We determined the release of lactate dehydrogenase as marker of injury and hydrogen peroxide (H₂O₂) and 8-isoprostane (8-IP) as sign of oxidative stress. Cells were also examined after trypan blue and nuclear DNA staining with 4′,6-diamidino-2-phenylindole to determine their membrane integrity and apoptosis respectively. Exposure of cells to 5 or 10 mM/L of Ca^++, for up-to 6 h, resulted in increased trypan blue and DAPI staining and production of H₂O₂. Similarly an exposure to CaOx crystals also resulted in increased trypan blue and DAPI staining and H₂O₂ production. An exposure to 5 mM/L Ca or CaOx crystals also resulted in increased production of 8-IP. A combination of the two treatments, Ca and CaOx crystals, did not show anymore changes than exposure to high Ca or CaOx crystals alone, except in the case of a longer exposure of 12 h. Longer exposures of 12 h resulted in cells sloughing from the substrate. These results indicate that exposure to high levels of Ca or CaOx crystals is injurious to renal epithelial cells but the two do not appear to work synergistically. On the other hand, results of our earlier studies suggest that oxalate and CaOx crystals work in synergy, i.e., CaOx crystals are more injurious in the presence of high oxalate. Perhaps Ox and CaOx crystals activate different biochemical pathways while Ca and CaOx crystals affect the identical pathways. This article directly relates to material presented at the 11th International Urolithiasis Symposium, Nice, France, 2–5 September 16-09-2008, from which the abstracts were published in the following issue of Urological Research: Urological Research (2008) 36:157–232. doi:.     

尿液成分对草酸钙结石的影响

目的 探讨尿液成分对草酸钙尿结石形成的影响。方珐 应用红外光谱仪对50份尿结石标本进行成分检测；对16例一水草酸钙（COM）与10例二水草酸钙（COD）尿结石患者的24h尿液进行生化检测，并比较两组生化指标。结果 87．5％的c0M结石患者和90％的c0D结石患者24h尿量减少；COM结石患者尿钙（4．94±2．11）mmol／24h，COD结石患者尿钙（9．43±3．78）mmol／24h；差异有统计学意义（P〈0．01）；COM结石患者尿磷（20．50±8．76）mmol／24h，COD结石患者尿磷（28．38±10．21）mmol／24h，差异有统计学意义（P〈0．05）；87．5％的COM结石患者尿枸橼酸低于正常水平。结论 COD结石患者尿钙、尿磷高于COM结石患者，表明COD结石的形成与高钙尿和高磷尿有关；COM结石的形成可能与低尿枸橼酸有关。