经鼻给予丙酸睾丸酮增加大鼠中脑5羟色胺能神经元的表达

目的:观察经鼻给予丙酸睾丸酮(TP)后大鼠中缝背核色氨酸羟化酶(TPH)及中缝背核、尾壳核与伏核5羟色胺(5-HT)和5羟色胺转运体(SERT)表达的改变.方法:对正常成年雄性及去势大鼠经鼻给予TP 21 d,利用免疫组织化学观察给药后大鼠中缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的免疫反应强度变化.结果:大鼠去势处理降低中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达;去势大鼠经鼻给予TP则可提高巾缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的表达,但未达到假手术水平;正常大鼠鼻腔给予TP后,中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达也显著增加.结论:经鼻给予TP增加大鼠中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达,为经鼻给予TP辅助治疗衰老过程中出现的运动相关行为障碍及抑郁症状提供实验依据.     

鼻腔给予丙酸睾丸酮对大鼠行为及中脑多巴胺能神经元的影响

目的:观察鼻腔给予丙酸睾丸酮(TP)后大鼠行为以及黑质纹状体酪氨酸羟化酶(TH)和多巴胺转运体(DAT)表达的改变.方法:对正常成年雄性及去势大鼠鼻腔给予TP 21d,分别利用开放广场实验和免疫组织化学技术观察给药后大鼠的行为及黑质和尾壳核TH及DAT的免疫反应强度变化.结果:开放广场实验结果显示正常大鼠鼻腔给予TP后水平运动得分、垂直运动得分、运动总径长比正常对照组增加;去势大鼠鼻腔给予TP后上述行为比去势组增加,但仍低于正常对照组.免疫组织化学结果显示正常大鼠鼻腔给予TP后黑质和尾壳核的TH及DAT免疫反应强度高于正常对照组;去势大鼠鼻腔给予TP后黑质和尾壳核的TH及DAT免疫反应强度高于去势组,但未达到正常对照组.结论:鼻腔给予TP增加大鼠的运动行为以及黑质和尾壳核TH和DAT的表达.     

丙酸睾丸酮早期处理对大鼠行为及脑内多巴胺转运体的影响

目的:观察丙酸睾丸酮早期处理对大鼠行为及脑内多巴胺转运体的影响.方法:分别以开放广场实验及免疫组织化学技术观察丙酸睾丸酮处理大鼠行为及脑内多巴胺转运体(DAT)的变化.结果:开放广场实验显示早期注射丙酸睾丸酮可使大鼠活动增多,表现为水平运动、垂直运动、运动的总径长以及清洁动作次数显著增加;免疫组织化学显色结果表明丙酸睾丸酮处理组大鼠黑质和尾壳核DAT免疫反应强度增强,其灰度值显著低于对照组.结论:丙酸睾丸酮早期处理大鼠活动的增加可能与雄激素影响黑质-尾壳核多巴胺能神经体系有关.     

丙酸睾丸酮早期处理对大鼠脑内5-羟色胺及其转运体的影响

目的:观察丙酸睾丸酮(TP)早期处理对大鼠脑内5-羟色胺(5-HT)及其转运体(SERT)的影响.方法:对生后第7天(PND7)的雄性Wistar乳鼠皮下注射TP至生后第21天(PND21),利用免疫组织化学和免疫印迹法观察生后第49天(PND49)实验大鼠中缝背核和尾壳核5-HT及SERT表达的变化.结果:免疫组织化学结果显示TP早期处理增加大鼠中缝背核和尾壳核处5-HT和SERT的免疫反应强度,中缝背核和尾壳核5-HT的灰度值比对照组分别降低了11.38%和7.90%,SERT的灰度值比对照组分别降低了6.79%和8.81%;免疫印迹结果显示TP早期处理增加大鼠脑内中缝背核和尾壳核处SERT的表达,中缝背核和尾壳核处SERT与β-actin相对吸光度比值比对照组分别升高了86.06%和26.29%.结论:TP早期处理影响大鼠脑内5-HT能神经,导致中缝背核和尾壳核5-HT和SERT增加.     

睾丸酮与葡萄糖酸钙联合用药对类固醇性骨质疏松雄性大鼠骨代谢的影响

目的探讨睾丸酮与葡萄糖酸钙联合用药对类固醇性骨质疏松雄性大鼠骨代谢过程的影响。方法30只3月龄SD雄性大鼠,随机分成年龄对照组(A组)、泼尼松组(B组)、实验组(C组)。A组予生理盐水灌胃(4mL.kg-1.d-1),B组予醋酸泼尼松灌胃(4mg.kg-1.d-1),C组灌胃给予甲睾酮(0.2mg.kg-1.d-1)+葡萄糖酸钙(0.5mg.kg-1.d-1)+醋酸泼尼松(4mg.kg-1.d-1),共90d。实验结束后,处死全部大鼠,取尺骨和血清做生化指标测定。结果B组大鼠尺骨羟脯氨酸的含量无显著变化,骨钙、骨磷、骨锌的含量显著降低;血钙显著升高,碱性磷酸酶含量降低。C组大鼠骨钙、骨磷、骨锌含量较B组显著升高;血钙降低恢复正常,碱性磷酸酶浓度升高,各项指标均接近正常对照组水平。结论睾丸酮与葡萄糖酸钙联合应用可以有效地防治泼尼松引起的雄性大鼠骨代谢紊乱。     

经鼻腔给予丙酸睾丸酮对老年大鼠骨骼肌的改善作用

目的:探讨经鼻腔给予丙酸睾丸酮对老年大鼠骨骼肌生理功能和形态结构的改善作用.方法:老年雄性大鼠经鼻腔给予丙酸睾丸酮12周,利用倾斜面实验和水平绳实验观察大鼠的行为变化;H-E染色显示大鼠肱二头肌的形态变化.结果:老年大鼠鼻腔给予丙酸睾丸酮对体质量无明显影响;老年大鼠连续2d的倾斜面下滑角度减小,50°角下滑次数增加,水平绳悬挂时间缩短,鼻腔给予丙酸睾丸酮后连续2d的倾斜面下滑角度增加,50°角下滑次数减少,水平绳悬挂时间延长;老年大鼠单位面积内肱二头肌肌细胞间隔的比例增多,鼻腔给予丙酸睾丸酮后单位面积内肱二头肌肌细胞间隔的比例减少.结论:鼻腔给予丙酸睾丸酮可以提高老年大鼠的平衡反应能力和肌张力,增加肱二头肌肌细胞面积,对老年大鼠肌细胞的生理功能及形态结构起到一定的保护作用,为鼻腔应用丙酸睾丸酮治疗老化过程引起的肌肉减少症提供实验依据.     

睾丸酮对雄性大鼠类固醇性骨质疏松的影响

目的探讨睾丸酮对雄性大鼠类固醇性骨质疏松的影响。方法30只3月龄雄性SD大鼠,随机分成对照组(A组)、泼尼松组(B组)、睾丸酮(C组)。A组灌生理盐水(4mL·kg-1·d-1),B组予醋酸泼尼松灌胃(4mg·kg-1·d-1),C组灌胃给予甲睾酮(0.2mg·kg-1·d-1)+醋酸泼尼松(4mg·kg-1·d-1),共90d。实验结束后,处死全部大鼠取腰椎和胫骨上段进行不脱钙骨包埋切片,应用计算机自动图像分析系统进行骨组织形态计量学分析。结果与泼尼松组比较,胫骨上端松质骨的%Tb.Ar增加了108%(P<0.01),Tb.N增加了96%(P<0.05),Tb.Sp减少60%;BFR/TV增加了172%(P<0.05),Oc.N减少40.7%(P<0.05);腰椎松质骨的%Tb.Ar增加了52.4%(P<0.05),Tb.Th增加了42%(P<0.05),Tb.Sp减少20%(P<0.05),MAR增加26%(P<0.05)。结论睾丸酮可以有效阻止泼尼松所引起的骨骨质丢失,维持正常的骨质结构。     

APP17肽对卵巢去势大鼠海马神经元退行性变的作用

目的 通过观察APP17肽对卵巢去势大鼠海马神经元退行性变的作用。证实APP17肽对神经元退行性变的改善作用。方法 雌性大鼠，行双侧卵巢切除手术造模。并于6周后皮下注射APP17肽进行治疗。手术后12周行水迷宫实验，至13周取血并行灌注固定，取脑海马组织作超薄切片电镜分析，并作冰冻切片进行雌激素受体（ERα），神经生长因子（NGF）及脑源性神经生长因子（BDNF）免疫组织化学染色，并用全自动化学发光免疫分析仪测定血清雌二醇水平。结果 卵巢去势组大鼠血清雌二醇水平降低。水迷宫检测卵巢去势组大鼠较正常组游完全程所须时间明显延长，错误反应次数明显增多，海马神经元超微结构出现明显损害；海马光镜观察发现ERα表达增多，NGF及BDNF表达减少，使用APP17肽治疗后并不改变血清雌二醇水平，但能明显改善海马神经元超微结构的损害，使上述有关蛋白质的表达恢复到正常水平。结论 APP17肽不同通过改变雌激素水平来发挥改善神经元功能减退的作用。而可能是通过神经营养因子起作用。     

不同张力扩张子宫颈诱导大鼠延髓内脏带c-Fos及神经型一氧化氮合酶的表达变化

目的观察不同张力扩张子宫颈(UCD)诱导大鼠延髓内脏带神经元c-Fos和神经型一氧化氮合酶(n NOS)的表达变化,探讨UCD疼痛在延髓水平的传导机制。方法成年雌性SD大鼠随机分为对照组(UCD 0g)、宫颈扩张50g张力组(UCD 50g)和宫颈扩张100g张力组(UCD 100g)。UCD组大鼠实施50g及100g张力扩张刺激,UCD刺激后2h,取延髓组织采用还原型辅酶Ⅱ(NADPH)组织化学和c-Fos免疫组织化学双重染色法观察c-Fos、n NOS和c-Fos/n NOS阳性神经元的分布,Western blotting和Real-time PCR法分别检测c-Fos及n NOS蛋白和mRNA水平。结果 c-Fos免疫阳性神经元的细胞核为棕黄色,呈圆形或卵圆形,胞质不着色。n NOS阳性神经元的胞体和突起呈蓝色,胞核不着色,呈空泡状。c-Fos/n NOS双标神经元的胞体和树突染成蓝色,细胞核呈棕黄色,这些神经元主要分布于延髓孤束核(NTS)和外侧网状核(LRN)内。与UCD 0g组相比,UCD 50g组和UCD 100g组大鼠NTS和LRN内c-Fos、n NOS以及c-Fos/n NOS阳性神经元数量明显增加,染色明显加深,c-Fos、n NOS蛋白及mRNA水平均明显升高(P0.01)。结论大鼠急性UCD可导致NTS和LRN神经元c-Fos及n NOS张力依赖性表达增加,NTS和LRN内的n NOS阳性神经元可能参与UCD疼痛在延髓水平的传导。     

睾丸酮对鼠脑皮质胆碱能纤维损伤后再生的影响

用2月龄去势雄性SD大鼠28只，建立皮质损伤模型，采用AChE染色法，通过计算切口两侧纤维数观察了睾丸酮对鼠脑皮质胆碱能纤维损伤后再生的影响。结果：损伤1周后用药组的损伤切口吻侧区的纤维密度明显高于损伤1周后的对照组和正常组（P＜0．01）；2周后，用药组纤维密度虽仍高于同期对照组（P＜0．01），但较1周时的密度明显降低；4周后用药组吻侧纤维密度较2周时升高，但与同期对照组差别不明显。同时也看到1周用药组损伤切口尾侧区的纤维密度甚低，明显低于正常值（P＜0．01），与同期报伤对照组差别不明显；2周和4周用药组尾侧区纤维密度增加高于对照组（P＜005）。提示：睾丸酮对鼠脑皮质损伤后胆碱能纤维再生有促进作用。     

Serum testosterone measurements

Serum testosterone and especially free testosterone is one of the parameters commonly used to evaluate androgen excess or deficiency. The authors equilibrated serum samples with 14C-labeled testosterone followed by an ammonium sulfate precipitation to compare the "apparent free testosterone concentration" with "total" serum testosterone concentration in the following populations: normal males and females; females presenting with gynecologic problems, particularly hirsutism and/or virilization; and males and females on maintenance hemodialysis. Total serum testosterone for each specimen was assayed with five different commercially available RIA kits encompassing a variety of technics: direct assay technics, assays utilizing extraction procedures prior to RIA; tritium-labeled tracer as well as iodine-labeled tracers. Clinical correlations improve strikingly when apparent free testosterone concentrations rather than total serum testosterone concentrations are used.     

Membrane mechanisms of action of testosterone

Laboratory of Physiology, Institute of Gerontology, Kiev. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 6, pp. 565–567, June, 1992.     

Safety of testosterone use in women

Female sexual desire appears to be in part androgen dependent, which has lead to the use of testosterone in women for low libido. Despite this benefit, the long-term safety of testosterone as a hormone replacement or therapy has not been well established. Side effects of testosterone therapy include mild and reversible acne and hirsuitism, as well as changes to the lipid profile with oral, but not transdermal testosterone. Short-term studies, up to 2 years, have shown that for serum plasma testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women, testosterone does not increase the risk of hepatotoxicity, endometrial hyperplasia, or behavioral hostility. No adverse cardiovascular effects including changes in blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, and polycythemia have been shown. Data is mixed with outcomes of breast cancer risk, with some experimental studies suggesting a decrease in estrogen-induced breast epithelial proliferation with low dose testosterone. Additionally, models of superphysiologic testosterone levels, such as polycystic ovarian disease, have not shown an increased risk of breast cancer. As with all hormone therapy in postmenopausal women, testosterone therapy should be individualized and requires that each woman weigh the risk and benefits. Nevertheless, only long-term safety studies will provide conclusive evidence as to testosterone safety in women.     

Receptivity in female hamsters following neonatal testosterone, testosterone propionate, and MER-25

One purpose of the present study was to determine the effectiveness of neonatally administered testosterone (T) and testosterone propionate (TP) in suppressing female behavior when their duration of action was equalized. A second aim was to evaluate whether suppression of female capacity associated with neonatal androgen would be lessened by an estrogen blocking agent. Eighty-seven hamsters were assigned to one of 8 groups which had a 3 mm Silastic pellet containing either T or TP as 0, 1, 3, or 9% of its weight present from the second through the tenth day after birth. An antiestrogen, MER-25, or oil was injected from Days 2–10 in another 66 animals that had 0 or 9% T or TP Silastic. Degree of ovarian and behavior suppression was proportional to androgen dosage; at each dosage, T was more effective than TP. MER-25 did not alter suppression produced by either androgen. It was concluded that the comparatively low level of action of exogenous T during development was due to its short half life and that estrogen might not be the hormone mediating suppression of female capacity.     

Dominance and testosterone in women

Fifty-two young women completed the Simple Adjective Test (a questionnaire designed to measure dominance) and at the same time provided 5 ml blood for testosterone assay. Higher dominance scores were associated with higher serum testosterone levels (t-test P<0.008).     

Ovarian testosterone secretion during perimenopause

Objective: The aim of the study was to investigate ovarian testosterone secretion during the last few years of reproductive life and after menopause. Materials and methods: Ovarian and peripheral venous levels of total testosterone were analyzed in 52 women aged 42–69 years (mean 51) undergoing hysterectomy with adnexal removal for benign indications at the Department of Obstetrics and Gynecology at Tampere University Hospital, Finland. The study population was divided into pre- (n=19), peri- (n=18) and postmenopausal (n=15) women in addition to the classical division according to menstrual cycle. Corresponding serum estradiol, progesterone and gonadotropin levels were measured, and the degree of ovarian stromal hyperplasia was analyzed. Results: The levels of all steroid hormones were higher in the ovarian vein than in the periphery. A significant positive correlation was found between age and ovarian vein testosterone levels (r=0.3, P=0.01). In premenopausal women, it was 1.5 nmol/l (median; range 0.78–6.0), in perimenopausal women 2.2 nmol/l (range 0.9–13.6), and 2.5 nmol/l (range 0.6–26.6) in postmenopause, respectively. Peripheral testosterone level did not increase with age. Ovarian stromal hyperplasia was significantly associated with increased testosterone secretion (P=0.009). Conclusion: The ovary seems to increase the secretion of testosterone into circulation during the menopausal transition period, as the highest levels were measured in postmenopausal women. High testosterone levels in the ovarian vein, however, were not reflected in the peripheral venous blood.     

Analysis of salivary testosterone by liquid chromatography-tandem mass spectrometry: correlation with serum bioavailable testosterone and aging

PURPOSE: To demonstrate that the salivary testosterone (T) concentration measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) is a sensitive biomarker of serum bioavailable testosterone (bio T) concentration and it's decrease with age. METHOD: Saliva and blood samples were collected from healthy 53 Japanese men (16-66yr) three times a day (9: 00-10: 00, 13: 00-14: 00, 17: 00-18: 00). Salivary T and serum total T levels were compared with serum bio T levels fractionated with concanavaline A. All samples were measured by LC-MS/MS. The stability of salivary T concentrations stored at -70 degrees C for 2 months was also examined. RESULTS: Salivary T levels correlated with bio T(r=0.88, n=158) better than total T did (r=0.71, n=159). The decrease of T concentration with age was observed in saliva of each sampling time. In total T, the decrease with age was weaker and was insignificant in the late afternoon. Salivary T was stable for 2 months at -70 degrees C and a freeze/thaw cycle (difference: average 3.7%, SD=8.4%, n=84). CONCLUSIONS: Salivary T measured by LC-MS/MS is a reliable biomarker of T availability and its decrease with aging.     

雄激素对家兔动脉粥样硬化的影响

目的：探讨雄激素在兔动脉硬化模型中是否 具有抗动脉硬化的作用。方法： 37只哈尔滨大耳白兔，饲以高脂饮食， 作如下分组：去势组：切除双侧睾丸；睾酮Ⅰ组：切除双侧睾丸并给予外源性雄激素0.25 mg·kg-1·d-1；睾酮Ⅱ组：切除双侧睾丸并给予外源性雄激素2.5 mg· kg -1·d-1；睾酮Ⅲ组：切除双侧睾丸并给予外源性雄激素12.5 mg·kg-1 ·d-1；假手术组。3个月后检测血中睾酮含量、血脂(包括TG、LDL-C、HDL-C)浓度、 PAI活性、一氧化氮(NO)、内皮素(ET)、血管紧张素Ⅱ(AngⅡ)含量。结果：去势组血清睾酮含量明显低于其它组； TG、LDL-C同其它组相比无显著差异，而HDL-C明 显降低； NO2-/NO3-含量低于其它组，而PAI活性、ET、AngⅡ却高于其它组。结论： 在高脂饮食诱发的兔动脉硬化模型中，雄激素可以发挥一定抗动脉硬化 的作用。