The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002     

不同剂量雌激素对裸鼠血管瘤模型的影响

目的：建立人毛细血管瘤裸鼠移植模型,探讨血管瘤裸鼠模型建立的最佳条件。方法：将手术切除的1例雌激素受体阳性的儿童增生期血管瘤组织制成组织块,植入20只裸鼠（BALB/cnudemice）皮下,每只4处,将20只裸鼠分为4个实验组。实验1组在移植后给予普通鼠食喂养;实验2组在1组基础上每周肌注雌二醇0.01mg;实验3组在1组基础上每周肌注雌二醇0.1mg;实验4组在1组基础上每周肌注雌二醇1mg,于移植后第30、60、90天切取移植瘤。移植瘤标本进行病理学光镜检查,用血管内皮细胞单克隆抗体CD31、CD34进行免疫组化染色。结果：移植后早期各组标本内皮细胞大量变性、坏死,30天后,单纯喂养的实验1组及实验2组部分移植瘤开始吸收或形成脓肿及纤维化。实验3、4组移植瘤开始缓慢生长。90天后实验1组、实验2组移植瘤均未成活,实验4组移植瘤部分成活,而实验3组移植瘤全部成活。光镜下成活的移植瘤与原血管瘤组织生物学特点相似。结论：不同剂量的雌激素对血管瘤裸鼠移植模型的建立有一定影响,适量的应用雌激素可建立稳定的人血管瘤裸鼠移植动物模型。该模型可以应用到基础和临床的血管瘤研究。     

绝经前、后女性骨代谢指标与白介素-1β受体拮抗剂的关系

目的探讨白介素-1β及其受体拈抗剂在绝经后女性骨代谢中的作用。方法选择绝经后女性128名,绝经前女性47名。用酶联免疫法测定受试者血清白介素-1β（IL-1β）、IL-1受体拮抗剂（IL-1Ra）、血清骨钙素（BGP）、尿I型胶原C末端肽（CTX）水平。用放射免疫法测定总雌二醇（E2）。结果绝经后女性组受试者L24、股骨颈、大转子的骨密度、E2、IL-1Ra／IL-1β比值和BGP较绝经前女性低,但CTX较高。L24、股骨颈骨密度、BGP与IL-1Ra／IL-1β旱正相关（r=0．709、r=0．801、r=0．729,P=0．023、P=0．021、P=0．005）。L24、股骨颈、大转子骨密度与IL-1β负相关（r=-0．855、r=-0．921、r=-0．725,P=0．002;P=0．005、P=0．024）。CTX与IL-1Ra／IL-1β负相关、与IL-1β正相关（r=-0．774,P=0．037;r=-901,P=0．036）。IL-1Ra与IL-1β正相关（r=0．981,P=0．005）。L24、大转子骨密度、BGP与E2正相关（r=0．664、r=0．700、r=0．621,P=0．012、P=0．003、P=0．009）。IL-1Ra、IL-1Ra／IL-1β与E2正相关（r=0．874,P=0．004;r=0．802,P=0．024）。结论绝经后女性骨代谢处于高分解、低合成的负平衡状态,性激素水平降低影响IL-1Ra与IL-1β的平衡可能起重要作用。     

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 group compared to the Milk group related to endocrine/metabolic disorders. However, little overlap was observed between the other treatment groups. These data suggest soy formula is not estrogenic in the male neonatal piglet and that soy formula does not significantly alter male reproductive development.     

定志小丸对雌性抑郁模型大鼠海马结构的影响

目的围绕海马结构的形态学研究定志小丸的抗抑郁机制。方法40只雌性大鼠分为对照组、抑郁症模型组（模型组）、蒸馏水组（DW组）和定志小丸组（中药组），Open field法检测行为学得分，ELISA法检测血清皮质醇和雌二醇（E2）含量，HE染色和电镜技术观察海马CA3区神经元形态，免疫组化技术检测齿状回神经干细胞（NSC）增殖。结果与对照组比较，模型组和DW组行为学得分及血清E2含量显著下降，皮质醇水平升高和NSC增殖明显降低，海马CA3区神经元损伤明显；中药组行为学得分和血清E2含量无明显变化，皮质醇明显减少，NSC增殖显著增加，海马CA3区神经元基本正常。结论定志小丸能够保护海马结构，这可能是其抗抑郁机制之一。     

蛇床子素对动物体内雌二醇和脂酶的影响及其相互关系的研究

目的观察蛇床子素对体内血脂、雌二醇(E2)和脂酶的影响及其相互关系。方法在建立高脂血症小鼠模型的同时,分组给予蛇床子素10～40mg.kg-1,3wk后测定肝素化后血浆LPL和HL活性及血浆TC、TG和HDL-C水平。分组给予正常小鼠蛇床子素10～40mg.kg-1,1wk后用ELISA方法观测血清E2水平的变化。建立去卵巢大鼠模型,给予蛇床子素10mg.kg-1,12wk后测定血清E2、TC和TG水平。结果给予蛇床子素10～20mg.kg-1后,能升高高脂血症小鼠肝素化后血浆LPL、HL活性和正常小鼠血清E2水平(P<0.05或P<0.01),也可使高脂血症小鼠血浆TC、TG和LDL-C降低(P<0.05或P<0.01),升高HDL-C(P<0.01)。蛇床子素剂量增至40mg.kg-1时,虽能升高正常小鼠血清E2水平(P<0.01),但高脂血症小鼠的血浆LPL、HL活性反而降低,对降低血浆TC、TG、LDL-C和升高HDL-C水平的幅度也不如低剂量的蛇床子素。去卵巢大鼠给予蛇床子素10mg.kg-1后,能增加血清E2水平(P<0.05),也能降低血清TG水平(P<0.05),TC的水平也有一定的降低。结论较低剂量的蛇床子素可通过增加血中E2水平,提高LPL和HL活性而降低血脂水平,较高剂量的蛇床子素虽可进一步增加血中E2水平,但LPL和HL活性反而降低,导致调脂作用减弱。     

经前平颗粒对经前期综合征肝气逆证模型大鼠下丘脑

目的:研究经前平颗粒对经前期综合征肝气逆证模型大鼠下丘脑中雌二醇α受体和孕酮受体表达的影响。方法:以情志刺激多因素法复制经前期综合征肝气逆证大鼠模型,经前平颗粒预防给药(10 g.kg-1,灌胃给药,连续5 d),采用免疫荧光细胞化学技术结合流式细胞仪检测大鼠下丘脑中雌二醇α受体和孕酮受体的蛋白表达量。结果:模型组大鼠下丘脑中雌二醇α受体和孕酮受体蛋白表达量与正常组相比显著降低(P<0.01),经前平颗粒组下丘脑中雌二醇α受体和孕酮受体蛋白表达量较模型组显著升高,接近于正常水平。结论:经前平颗粒可以上调下丘脑雌二醇α受体和孕酮受体蛋白表达水平,这可能是其治疗经前期综合征肝气逆证的作用机制之一。     

吗啡对体外培养的人乳腺细胞雌激素受体mRNA表达的影响

目的：研究吗啡对雌激素诱导的体外培养人的正常乳腺细胞的雌激素受体（ER）mRNA表达的影响。方法：购买人正常乳腺纤维细胞株进行培养，给予17-β雌二醇（E2），吗啡（Mor）及纳洛酮干预。通过RT—PCR的方法半定量分析吗啡对正常乳腺细胞ER mRNA表达的影响。结果：ER与内参照B—actin分别在249 bp和270 bp处出现特征性条带。雌激素组、吗啡组与对照组比较，差异有显著性（P〈0．05），E2＋Mor组与对照组比较，差异无显著性（P〉0．05）。吗啡作用24h呈剂量依赖性抑制乳腺细胞ERmRNA的表达，3组吗啡的终浓度分别为1×10^-6mol／L、1×10^-5mol／L、1×10^-4 mol／L，差异有显著性（P〈0，05）。结论：从mRNA水平证明了外源性阿片类药物吗啡可直接影响雌激素对乳腺的促增殖作用，同时还可剂量依赖性下调雌激素受体mRNA的表达。     

中药分型治疗更年期综合征95例疗效观察

目的探讨中药分型加减治疗更年期综合征的有效方法。方法将190例患者随机分为两组对比观察，治疗组应用中药分型加减治疗，每日1剂，对照组应用更年康治疗，4周后评价疗效。结果治疗组95例中痊愈率21．1％（P〈0．05）；治疗组治疗前后各主要症状评分比较均有统计学意义（P〈0．05-0．01），且明显优于对照组（P〈0．05-0．01）；并发现有明显提高患者血清雌二醇水平作用（P〈0．05）。结论中药分型加减治疗更年期综合征疗效可靠。