外源性睾酮对去睾丸家兔性激素以及血脂和载脂蛋白水平的影响

目的 :探讨不同剂量的外源性睾酮对去势 (双侧睾丸切除 )雄性家兔性激素以及血脂和载脂蛋白水平的影响。方法 :成熟雄性新西兰白兔 40只 ,随机分成 5组 (n =8) :对照组、单纯去势组、低睾酮血症组 [去势后肌注十一酸睾酮 (TU) ,3mg/kg ,每 2周一次 ]、生理水平组 (去势后肌注TU ,6mg/kg ,每 2周一次 )及高睾酮血症组 (去势后肌注TU ,1 2mg/kg ,每 2周一次 )。 8周后测量血清总睾酮 (TT)、雌二醇 (E2 )、脱氢表雄酮 (DHEA)及总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C) ,低密度脂蛋白胆固醇 (LDL C) ,甘油三酯 (TG) ,载脂蛋白A1 (ApoA1 ) ,载脂蛋白B(ApoB)。结果 :雄兔血清TT水平在去势后明显下降至极低水平 ,明显低于对照组 (P <0 .0 1 ) ,3mg/kgTU补充后轻度升高 ,仍明显低于对照组 (P <0 .0 1 ) ,形成低睾酮血症 ,6mg/kgTU补充后与对照组相比无显著差异 (P >0 .0 5) ,接近生理水平 ,1 2mg/kgTU补充后明显高于对照组和低睾酮血症组 (P均 <0 .0 1 ) ,形成高睾酮血症。血清E2 水平在对照组和生理水平组相近并且最低 ,单纯去势组和低睾血症组相近 ,高睾酮血症组最高。E2 /TT比值在对照组和生理水平组相近并且最小 ,在单纯去势组最大 ,低睾酮血症组大于高睾酮血症组。单纯去势组、低睾酮血症组和高睾酮血症     

GnRH-A主动免疫家兔的去势效果

为了探讨促性腺激素释放激素类似物(gonadotropin releasing hormone analogue,GnRH-A)对动物免疫去势的效果及作用机理.在30只日本大耳白兔(Oryctolagus cuniculus)(EG-Ⅰ与EG-Ⅱ组)的颈背部皮下分2.3点注射1.0ml(100/gml)自制的GnRH-A抗原乳剂,EG-Ⅱ组3周后加强免疫一次;测定睾丸长度与重量、体重、血清GnRH抗体效价及睾酮浓度.结果表明,EG-Ⅱ组睾丸长度与EG-I组差异极显著(P<0.01);EG-Ⅱ组的GnRH抗体水平明显高于EG-Ⅰ组;EG-Ⅱ组、EG-Ⅰ组与对照组的血清睾酮浓度差异逐渐增加,102 d时EG-Ⅱ组睾酮浓度极显著低于对照组(P<0.01),且第28 d后EG-Ⅱ组睾酮浓度显著低于EG-Ⅰ组(P<0.05);EG-Ⅱ组体重和日增重最大,显著高于EG-Ⅰ组及对照组(P<0.05).GnRH-A主动免疫家兔对睾丸发育、血清GnRH抗体效价和睾酮浓度具有显著的影响,加强免疫效果更理想.     

莪术油注射液对慢性低氧大鼠学习与记忆的影响

本文旨在探讨莪术油注射液对慢性低氧大鼠学习与记忆的影响及其可能机制.将Sprague.Dawley大鼠随机分为对照组、慢性低氧组、5 mg/kg体重莪术油组、10 mg/kg体重莪术油组、20 mg/kg体重莪术油组,每组14只.慢性低氧处理采用低氧舱内吸入大约10%O2、5%CO2,饲养10 h/d,持续饲养28 d.莪术油组大鼠低氧处理前腹腔注射相应浓度的莪术油注射液.实验结束次日,通过Morris水迷宫测试各组动物学习和记忆成绩的变化;测定各组大鼠血清和海马组织丙二醛(malonaldehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性以及海马组织Ca2 浓度([Ca2 i]);通过免疫组织化学和Western blot检测磷酸化Ca2 /钙调蛋白依赖性蛋白激酶Ⅱ(phosphorylated Ca2 /calmodulin-dependent pro-tein kinase Ⅱ,p-CaMKII)在海马组织和胞膜上的表达.结果显示,与对照组相比,慢性低氧组大鼠隐蔽平台的逃避潜伏期明显延长(P<0.05),血清和海马组织MDA含量明显增高,SOD活性显著降低(P<0.05,P<0.01),海马组织[Ca2 ]i明显增高(P<0.01),海马P-CaMKII表达量显著降低(P<0.01).与慢性低氧组比较,莪术油各组发生以下变化:10、20 mg/kg体重莪术油组大鼠隐蔽平台的逃避潜伏期显著缩短(P<0.05):5、10、20 mg/kg体重莪术油组大鼠血清和海马组织MDA含量均显著降低(P相似文献   

度他雄胺对大鼠附睾精子成熟和生育的影响

目的通过度他雄胺对大鼠附睾精子和生育的影响,探索调节雄性生育的睾丸后作用靶点。方法使用度他雄胺20和40 mg/(kg.d)大鼠灌胃给药,连续2周。给药结束后雄雌鼠按1∶2合笼,计算生殖指数;采用计算机辅助精子分析系统分析精子活力和形态;采用SYBR-14和PI双重荧光染色计算精子存活率;采用Elisa法测定大鼠睾酮(T)和双氢睾酮(DHT)血清浓度;采用HE染色法对各组睾丸、附睾进行组织学分析。结果度他雄胺低、高剂量组双氢睾酮浓度均显著下降,分别为0.54和0.28 nmol/L(P<0.01),精子活力明显降低,分别为39.0%和28.7%(P<0.01),畸形率分别增加为10.3%和15.6%(P<0.05),最后受孕率分别降为62.5%和38.4%。而睾酮水平和交配指数均无明显变化(P>0.05),睾丸和附睾亦无明显病理学改变。结论度他雄胺通过抑制DHT生成,影响附睾精子成熟而导致大鼠不育,为今后男性避孕和不育药物研发提供了新思路。     

不同剂量炔雌醚对雄性小鼠繁殖生理的作用

为探究不同剂量炔雌醚作用于雄性昆明小鼠时,对小鼠的繁殖生理指标的影响,现将18只雄性昆明小鼠分为3组:对照组(C组)、10 mg/kg给药组(E10组)、20 mg/kg给药组(E20组)进行实验。在给药后第6天进行剖检,测量其繁殖器官重量及血清睾酮浓度,观察其睾丸组织形态切片。结果发现,两给药组繁殖器官重量与对照组相比无明显差异;(E10组)血清睾酮浓度有所上升,(E20组)无明显变化;(E20组)曲细精管受到一定程度的损伤,而(E10组)的损伤不明显。因此,高浓度的炔雌醚可能对雄性昆明小鼠有更好的抗生育作用。本研究为进一步明确炔雌醚对鼠类不育控制的最佳浓度提供了一定的理论依据。     

不同移植部位对成年大鼠睾丸间质细胞雄激素分泌功能的影响

目的:探索不同移植部位对移植的成年SD大鼠睾丸中睾丸间质细胞存活及雄激素分泌功能的影响。方法:将健康成年雄性SD大鼠随机分为对照组、假手术组、皮下组和肾包膜组。对照组大鼠不去势,其余大鼠于睾丸移植前1周行去势手术。对照组和假手术组去势后仅行背部皮肤切开,不进行睾丸移植;皮下组背部两侧各移植1/3个成年SD大鼠睾丸组织;肾包膜组每侧肾包膜下移植1/3个成年SD大鼠睾丸组织。4周后取材行HE和免疫组化染色,分析移植睾丸组织中睾丸间质细胞存活情况,ELISA法检测受体大鼠血清睾酮水平。结果:皮下组和肾包膜组移植物中难于见到完整的睾丸间质组织,但免疫组化染色发现大量HSD-17β1阳性细胞,对照组、皮下组和肾包膜组的HSD-17β1阳性细胞数分别为(24.33±4.30)、(9.83±4.05)和(12.67±2.81)个,对照组与皮下组相比差异具有统计学意义(p0.05);ELISA分析发现对照组、假手术组、皮下组和肾包膜组的血清睾酮浓度分别为(3.81±1.32)、(0.28±0.08)、(0.44±0.13)和(0.90±0.31)ng/m L,肾包膜组血清睾酮浓度高于假手术组(p0.01)和皮下组(p0.05),而皮下组血清睾酮水平高于假手术组,但两者差异无统计学意义(p0.05)。结论:移植的成年大鼠睾丸组织中的睾丸间质细胞可在受体肾包膜下或皮下存活,但肾包膜下移植可能更加有利于睾丸间质细胞存活和雄激素分泌。     

瑞舒伐他汀对兔动脉粥样硬化斑块及血清PAPP-A的影响

目的:探讨瑞舒伐他汀对兔动脉粥样硬化斑块及血清妊娠相关血浆蛋白(PAPP-A)的影响.方法:新西兰家兔18只,随机分为正常对照组(Normal组,n=6)、动物粥样梗化模型组(AS组,n=6)和瑞舒伐他汀治疗组(RSV组,n=6).于治疗前、治疗后,检测血清总胆固醇(TC)、三酰甘油(TG)、血清低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)含量,酶联免疲吸附法(ELISA)检测血清PAPP-A水平.同时,用血管内超声检查(IVUS)测定病变部位的血管外弹力膜面积(EEMA)、管腔面积(LA)和斑块面积(PA),计算管腔面积狭窄百分率(LAS%).结果:治疗前,AS组和RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较Normal组高(P<0.01),HDL-C的水平较Normal组低(P<0.01);治疗后,RSV组兔的血清TC、TG、LDL-C及PAPP-A比AS组低(P<0.01).HDL-C的水平比AS组高(P<0.01),且RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较治疗前低(P<0.01),HDL-C的水平较治疗前高(P<0.01).血管内超声检查结果显示,治疗后,RSV组兔的LAS%(30.87%±5.27%)比AS组低(37.42%±6.12%)(P<0.01).结论:瑞舒伐他汀能改善对AS兔血脂,减少AS斑块形成及降低血清PAPP-A水平.     

菟丝子对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响

本文以大强度耐力训练大鼠为模型,对菟丝子对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响进行了研究.试验中分别以1.16、2.32、6.96 g.kg-1.d-1的剂量给大鼠灌胃42d,并进行负重游泳实验、血清睾酮等生化指标测定.结果显示,菟丝子各剂量组力竭游泳时间长于运动对照组(T组)(P＜0.01);血清睾酮高于T组(P＜0.01),血清皮质酮低于T组(P＜0.05);各组间血清睾酮与皮质酮比值变化与睾酮变化较为一致;肝糖原(P＜0.05)、肌糖原(P＜0.01)高于T组;血清尿素氮低于T组(P＜0.05);血红蛋白高于T组(P＜0.05).从而表明补充菟丝子可以减轻大鼠血睾酮、皮质酮受高强度运动量的影响,维持在正常生理水平;促进蛋白质合成,抑制氨基酸和蛋白质分解,提高血红蛋白含量和糖原的储备,增强抗疲劳能力,具有多靶点、多途径的显著特点.     

不同造模方法对大鼠多囊卵巢综合征模型的影响

目的采用不同方法诱导SD清洁级雌性大鼠多囊卵巢综合征(PCOS)动物模型,造模完成后检测大鼠血清相关激素并观察卵巢局部形态学改变,并探讨其意义。方法分别采用来曲唑、硫酸普拉睾酮钠、硫酸普拉睾酮钠联合HCG诱导大鼠PCO模型,RIA法测定血清LH、FSH、E2、P、T、PRL、INS水平,HE染色后光镜下观察卵巢局部形态。结果A组(对照组)和B组(来曲唑组)比较,B组较A组血清FSH浓度升高,血清P浓度降低,差异有统计学意义(P0.05);B组血清T浓度较A组明显升高,差异有显著统计学意义(P0.01)。D组(硫酸普拉睾酮钠组)与C组(对照组)比较,两组间血清性激素及INS差异无显著性(P0.05)。E组(硫酸普拉睾酮钠联合HCG组)与C组比较,E组血清T浓度、LH/FSH比值较C组升高,差异有统计学意义(P0.05)。E组与D组比较,血清P、T浓度升高,差异有统计学意义(P0.05)。A、C两组卵巢局部形态基本正常,可见发育成熟的卵泡及优势卵泡,B、D、E三组未见优势卵泡,均可见卵巢多囊样改变。结论使用来曲唑或硫酸普拉睾酮钠联合HCG诱导大鼠PCOS模型,无论在影响血清性激素还是卵巢局部形态学改变方面与临床表现很接近,符合动物PCOS造模要求。     

疏肝益阳胶囊联合万艾可对糖尿病男性性功能障碍患者血清睾酮、雌二醇水平及性功能的影响

目的:探讨疏肝益阳胶囊联合万艾可对糖尿病男性性功能障碍患者血清生殖激素睾酮(T)、雌二醇(E2)水平和性功能的影响。方法:选择2015年7月到2016年7月我院接诊的94例糖尿病男性性功能障碍患者,通过随机数表法分作观察组及对照组,每组47例。对照组使用万艾可进行治疗,观察组在其基础上加用疏肝益阳胶囊进行联合治疗。比较两组的临床疗效、治疗前后国际勃起功能指数-5(IIEF-5)问卷表测评评分、部分雄激素缺乏(PADAM)问卷评分、生殖激素睾酮(T)、雌二醇(E2)水平的变化。结果:治疗后,观察组的临床总有效率明显高于对照组(P0.05),IIEF-5评分显著高于对照组(P0.05),PADAM评分明显低于对照组(P0.05),血清T激素水平明显高于对照组(P0.05),血清E2激素水平明显低于对照组(P0.05),治疗组不良反应总发生率明显低于对照组(P0.05)。结论:疏肝益阳胶囊联合万艾可治疗糖尿病男性性功能障碍可有效提高临床疗效,改善患者性功能,可提高血清T水平,降低E2水平。     

Short-term androgen deprivation does not alter CaR and VDR mRNA expression in duodenal mucosa in male rats

Androgen deprivation is associated with decline in intestinal calcium absorption. The effect of androgen on CaR and VDR intestinal mucosa has not yet been studied. Calcium homeostasis, a real bone mineral density (aBMD, dual energy X-ray absorptiometry) and expression of CaR and VDR mRNA in duodenal mucosa of orchidectomized (ORX) and sham operated (Sham) adult Sprague Dawley rats at 4 week have been studied. There was no significant difference in serum calcium, alkaline phosphatase, calcidiol and calcitriol levels between both the groups. Serum testosterone (T) (ng/dl) and inorganic phosphorous (iP) (mg/dl) levels were significantly lower in ORX rats. As compared to sham rats, ORX rats had significant decline in in-vitro aBMD at proximal, middle and distal tibia, proximal, mid and distal femur and femoral neck (P < 0.05). Northern blot analysis revealed no significant alteration in the CaR and VDR mRNA expression in duodenal mucosa in ORX rats. CaR and VDR mRNA expression in duodenal mucosa is therefore, not affected by physiological concentrations of testosterone in rats.     

A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m² and 10.72 nmol/L, respectively.     

Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat.

Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D.     

Osteoporosis in male hypogonadism: responses to androgen substitution differ among men with primary and secondary hypogonadism

BACKGROUND: No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). METHODS: We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. RESULTS: At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (-1.52 +/- 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, -0.87 +/- 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 +/- 1.3%, testosterone enanthate +4.8 +/- 0.2%, testosterone undecanoate +3.4 +/- 2.5%, mesterolone +0.8 +/- 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. CONCLUSIONS: In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.     

Relationship between Body Mass Composition,Bone Mineral Density,Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis

A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content.     

Bone metabolism in patients with primary hyperparathyroidism before and after surgery

Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.     

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.     

Testosterone treatment increases thromboxane function in rat cerebral arteries

We previously showed that testosterone, administered in vivo, increases the tone of cerebral arteries. A possible underlying mechanism is increased vasoconstriction through the thromboxane A2 (TxA2) pathway. Therefore, we investigated the effect of chronic testosterone treatment (4 wk) on TxA2 synthase levels and the contribution of TxA2 to vascular tone in rat middle cerebral arteries (MCAs). Using immunofluorescence and confocal microscopy, we demonstrated that TxA2 synthase is present in MCA segments in both smooth muscle and endothelial layers. Using Western blot analysis, we found that TxA2 synthase protein levels are higher in cerebral vessel homogenates from testosterone-treated orchiectomized (ORX + T) rats compared with orchiectomized (ORX) control animals. Functional consequences of changes in cerebrovascular TxA2 synthase were determined using cannulated, pressurized MCA segments in vitro. Constrictor responses to the TxA2 mimetic U-46619 were not different between the ORX + T and ORX groups. However, dilator responses to either the selective TxA2 synthase inhibitor furegrelate or the TxA2-endoperoxide receptor (TP) antagonist SQ-29548 were greater in the ORX + T compared with ORX group. In endothelium-denuded arteries, the dilation to furegrelate was attenuated in both the ORX and ORX + T groups, and the difference between the groups was abolished. These data suggest that chronic testosterone treatment enhances TxA2-mediated tone in rat cerebral arteries by increasing endothelial TxA2 synthesis without altering the TP receptors mediating constriction. The effect of in vivo testosterone on cerebrovascular TxA2 synthase, observed here after chronic hormone administration, may contribute to the risk of vasospasm and thrombosis related to cerebrovascular disease.     

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.