复方更年康延缓老年骨质疏松雌性大鼠神经内分泌衰老的实验研究

目的研究更年康延缓老年骨质疏松雌性大鼠神经内分泌衰老的作用机制。方法通过用双能X线吸收技术进行骨密度测定,与正常青年雌性大鼠对比,选择有骨质疏松的老年雌性大鼠作为研究对象,分别用中药复方更年康和尼尔雌醇灌胃3个月,观察中药复方更年康对骨质疏松的治疗作用及对神经内分泌衰老的延缓作用。采用TUNEL法检测下丘脑弓状核神经元凋亡的情况,双能X线吸收技术(DEXA)检测骨密度,放射免疫法(RIA)检测血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)水平。结果老年雌性骨质疏松大鼠血清FSH、LH升高,E2下降,骨密度下降,下丘脑弓状核神经元凋亡增加,中药复方更年康能提高骨质疏松大鼠的骨密度,能使FSH、LH水平下降,而血清E2水平升高不明显,下丘脑弓状核神经元凋亡减少。结论复方更年康在治疗老年骨质疏松症时可以取得与雌激素替代治疗同样的治疗效果,在延缓衰老方面比雌激素替代治疗作用更显著,综合评价治疗效果,复方更年康优于雌激素替代治疗。     

复方更年康对老年雌鼠性激素及骨雌激素受体表达的影响

目的比较用复方更年康和雌激素替代两种方法治疗老年雌性骨质疏松症大鼠,分析性激素及雌激素受体在老年骨质疏松发病中的作用,以寻找治疗该病的理想方法。方法选择有骨质疏松的老年雌性大鼠作为研究对象,分为复方更年康组、尼尔雌醇组和对照组。采用3'末端原位标记法(TUNEL)检测卵巢颗粒细胞凋亡,放射免疫法(RIA)检测血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)水平,反转录-聚合酶链反应(RT-PCR)方法检测各组大鼠骨组织雌激素受体(ER)表达水平,双能X线吸收技术(DEXA)检测骨密度。观察复方更年康治疗该病的疗效。结果老年骨质疏松大鼠骨密度减少,血清E2水平下降,FSH、LH水平上升,下肢骨雌激素受体mRNA表达水平下降;复方更年康能提高骨质疏松大鼠的骨密度、骨组织雌激素受体mRNA表达水平,血清E2水平升高不明显,而使FSH、LH水平下降,同时抑制卵巢颗粒细胞的凋亡。结论复方更年康对老年雌性骨质疏松大鼠的作用,是通过抑制卵巢颗粒细胞凋亡,抑制性腺功能的进一步衰竭,调节内分泌紊乱,提高骨组织雌激素受体,增加骨密度。     

更年平调液对老年动物的免疫增强作用

目的：研究更年闰调液对免疫系统功能的影响。方法;采用免疫器官脏器指数、小鼠碳粒廓清和ＰＨＡ刺激淋转化等研究方法。结果：更年平调液能显著增另老年去势雌性大鼠脾、胸腺指数、增强老年小鼠单核细胞吞噬功能和ＰＨＡ刺激的淋巴细胞转化,并提高老年小鼠的耐寒和抗疲劳能力。结论：更年平调液有免疫增强作用。     

口服棉酚者血清中睾丸酮、促黄体生成素和卵泡素浓度的变化

棉酚是一种作用干睾丸的抗精子发生药物、损伤变态过程的精子细胞和中晚期精母细胞,近期亦有人报道棉酚能进一步损伤精原细胞与间质细胞,但棉酚对人垂体性腺轴系激素的影响报道不多。本文通过测定服用棉酚1～79个月的男子血中睾丸酮,LH和FSH含量的变化,探讨棉酚对人垂体性腺轴系的影响、观察棉酚对睾丸间质细胞及生精上皮的损伤作用。     

二甲双胍对大鼠垂体—性腺轴内分泌功能的影响

目的研究二甲双胍(Metformin,MF)对大鼠垂体-性腺轴内分泌功能的影响。方法采用放射免疫分析法和电子显微镜技术,系统研究MF对大鼠血清性激素含量及靶腺组织形态的影响。结果MF135mg·kg-1·d-1,ig,连续用药14d,可使♂大鼠睾酮(T)的含量及♀大鼠血清黄体生成素(LH)水平明显降低,而对♀大鼠卵泡刺激素(FSH)、雌二醇(E2)、孕酮(P)的含量和♂大鼠血清LH、FSH的含量均无影响。270mg·kg-1·d-1MF除明显降低♂大鼠血清T和♀大鼠血清LH的含量外,可使♀大鼠血清P、E2的含量升高(P<0.01)。电镜观察显示,大鼠睾丸内分泌细胞超微结构发生退行性改变,而卵巢细胞超微结构则呈现分泌旺盛的表现。结论MF对♀大鼠垂体-卵巢轴内分泌功能有促进作用,而对♂大鼠垂体-睾丸轴内分泌功能有抑制作用,且使靶腺内分泌细胞的超微结构出现相应的变化。     

海洛因依赖及戒断后雄性大鼠性腺轴组织病理学研究

规律腹腔注射海洛因建立♂大白鼠海洛因身体依赖模型（ｎ＝５），戒断后制成戒断模型（ｎ＝１０），并设对照组，对依赖组和戒断组大鼠的大脑、下丘脑、垂体、肾上腺、睾丸和附睾组织做光镜和电镜观察，结果发现依赖组的大脑皮质，下丘脑，垂体，睾丸和附睾均有明显的组织病理改变及超微结构改变，且短期戒断后这些改变仍持续存在。该文对海洛因依赖引起中枢神经系统及下丘脑－垂体－睾丸轴组织产生病理改变的机理作了探讨。     

海洛因依赖及戒断后雄性大鼠性腺轴组织病理学研究

规律腹腔注射海洛因建立♂大白鼠海洛因身体依赖模型（ｎ＝１５），戒断后制成戒断模型（ｎ＝１０），并设对照组。对依赖组和戒断组大鼠的大脑、下丘脑、垂体、肾上腺、睾丸和附睾组织做光镜和电镜观察，结果发现依赖组的大脑皮质、下丘脑、垂体、睾丸和附睾均有明显的组织病理改变及超微结构改变，且短期戒断后这些改变仍持续存在。该文对海洛因依赖引起中枢神经系统及下丘脑－垂体－睾丸轴组织产生病理改变的机理作了探讨。     

血清生殖激素、精浆锌与睾丸生精障碍的关系

目的探讨无精子症患者血清生殖激素水平、精浆锌含量与睾丸生精状态的关系.方法对128例男性不育患者与30例正常对照者,进行了血清生殖激素(FSH,LH,T,PRL)检测、睾丸活检病理学检查、睾丸容积及精液分析,测定了40例无精子症患者和30例正常对照精浆的锌含量.结果无精子症组的精浆锌含量降低,与正常对照组比较存在显著性差异(P《0.05);睾丸源性无精子症血清FSH,LH升高,睾丸容积减少,睾丸容积小于15ml者,其T/LH值下降,与正常对照组间存在非常显著性差异(P《0.01),提示睾丸功能损伤,间质细胞功能受损. 结论血清FSH含量在鉴别睾丸源发性与梗阻性无精子症中是非常重要的指标,T/LH比值是判定睾丸间质细胞损伤的指标,睾丸生精障碍程度愈严重,其FSH,LH水平愈高,而L/LH值降低愈明显,精浆Zn及血清生殖激素的检测,在男性不育无精子症诊断和在判定睾丸功能的损伤程度中具有重要作用.     

血清生殖激素、精浆锌与睾丸生精障碍的关系

目的 探讨无精子症患者血清生殖激素水平、精浆锌含量与睾丸生精状态的关系。方法 对128例男性不育患者与30例正常对照者,进行了血清生殖激素（FSH,LH,T,PRL）检测、睾丸活检病理学检查、睾丸容积及精液分析,测定了40例无精子症患者和30例正常对照精浆的锌含量。结果 无精子症组的精浆锌含量降低,与正常对照组比较存在显著性差异（P<0.05）;睾丸源性无精子症血清FSH,LH升高,睾丸容积减少,睾丸容积小于15ml者,其T/LH值下降,与正常对照组间存在非常显著性差异（P<0.01）,提示睾丸功能损伤,间质细胞功能受损。结论 血清FSH含量在鉴别睾丸源发性与梗阻性无精子症中是非常重要的指标,T/LH比值是判定睾丸间质细胞损伤的指标,睾丸生精障碍程度愈严重,其FSH,LH水平愈高,而L/LH值降低愈明显,精浆Zn及血清生殖激素的检测,在男性不育无精子症诊断和在判定睾丸功能的损伤程度中具有重要作用。     

赛庚啶对大鼠垂体-性腺轴功能的影响

目的　研究赛庚啶对大鼠垂体 性腺轴内分泌功能的影响。方法　用放射免疫分析法 (RIA)和电镜 ,观察赛庚啶对大鼠垂体 性腺轴内分泌功能及垂体促性腺细胞、卵巢、睾丸细胞超微结构的影响。结果　赛庚啶 2 .3mg·kg-1·d-1,ig ,连续用药14d ,可明显降低雌性大鼠血清卵泡刺激素 (FSH)、孕酮 (P)的含量 (P <0 .0 1) ,而升高黄体生成素 (LH)的水平 (P <0 .0 5 )。 4 .6mg·kg-1·d-1赛庚啶不但可引起雌性大鼠血清FSH、雌二醇 (E2 )、P的水平显著降低 ,升高LH的含量 (P <0 .0 5及 <0 .0 1) ,而且使雄性大鼠血清LH、T的含量明显升高 (P <0 .0 5 )。组织形态电镜观察 ,该药亦可引起大鼠卵巢细胞超微结构的退行性改变 ,睾丸支持细胞呈分泌状态 ,而垂体促性腺分泌细胞则无明显变化。结论　赛庚啶可抑制雌性大鼠FSH、E2 、P的分泌 ,促进雌、雄大鼠LH及雄性大鼠T的分泌 ,其机制可能与赛庚啶直接影响靶器官的分泌细胞有关。     

Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced surge of luteinizing hormone in female Sprague-Dawley rats without changing estrogen receptor action.

High oral doses of atrazine (ATRA) disrupt normal neuroendocrine function, resulting in suppression of the luteinizing hormone (LH) surge in adult, ovariectomized (OVX) estrogen-primed female rats. While the mechanism by which ATRA inhibits LH secretion is not known, current data indicate that ATRA does have anti-estrogenic properties in vitro and in vivo. In the body, ATRA is rapidly converted to diaminochlorotriazine (DACT). The present study was conducted to investigate the effects of ATRA and DACT on the estradiol benzoate (EB)/progesterone (P) induced LH surge and to determine if such changes correlate with impaired estrogen receptor (ER) function. ATRA, administered by gavage for five consecutive days to adult OVX, female Sprague-Dawley rats, caused a dose-dependent suppression of the EB/P induced LH surge. Although to a lesser degree than ATRA, DACT significantly suppressed total plasma LH and peak LH surge levels in EB/P primed animals by 60 and 58%, respectively. DACT treatment also decreased release of LH from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) by 47% compared to control. Total plasma LH secretion was reduced by 37% compared to control, suggesting that in addition to potential hypothalamic dysfunction, pituitary function is altered. To further investigate the mechanism by which hypothalamic function might be altered, potential anti-estrogenicity of ATRA and DACT were assessed by evaluating ER function treated rats. Using an in vitro receptor binding assay, ATRA, but not DACT, inhibited binding of [(3)H]-estradiol to ER. In contrast, ATRA, administered to female rats under dosing conditions which suppressed the LH surge, neither changed the levels of unoccupied ER nor altered the estrogen induced up-regulation of progesterone receptor mRNA. Collectively, these results indicate that although ATRA is capable of binding ER in vitro, the suppression of LH after treatment with high doses of ATRA is not due to alterations of hypothalamic ER function.     

Testicular toxicity induced by a triple neurokinin receptor antagonist in male dogs

Mechanism mediating the testicular toxicity induced by CS-003, a triple neurokinin receptor antagonist, was investigated in male dogs. Daily CS-003 administrations showed testicular toxicity, such as a decrease in the sperm number, motility and prostate weight; and an increase in sperm abnormality, accompanying histopathological changes in the testis, epididymis and prostate. A single CS-003 administration suppressed plasma testosterone and LH levels in intact and castrated males. The suppressed LH release was restored by GnRH agonist injection, suggesting that pituitary sensitivity to GnRH is not impaired by CS-003. Treatment with SB223412, a neurokinin 3 receptor antagonist, caused a similar effect to CS-003, such as toxicity in the testis, prostate and epididymis and decreased plasma level of LH and testosterone. In conclusion, CS-003-induced testicular toxicity is caused by the inhibition of neurokinin B/neurokinin 3 receptor signaling probably at the hypothalamic level in male dogs.     

Altered regulation of pituitary gonadotropin-releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases the potency of androgens as feedback inhibitors of luteinizing hormone (LH) secretion. Our objectives were to determine if this increase is due to pituitary or hypothalamic dysfunction (or both), and to investigate the mechanism by which TCDD produces this effect. Seven days after dosing, TCDD inhibited the compensatory increases in (i) pituitary gonadotropin-releasing hormone (GnRH) receptor number, (ii) LH secretory responsiveness of the pituitary to GnRH, and (iii) plasma LH concentrations which should have occurred in response to TCDD-induced decreases in plasma testosterone concentrations. TCDD did not inhibit these compensatory responses in the absence of testicular hormones, while treatment of castrated rats with testosterone restored the ability of TCDD to prevent these increases. These findings demonstrate that TCDD alters the androgenic regulation of pituitary GnRH receptor number and pituitary responsiveness to GnRH stimulation. The pituitary is therefore a target organ for TCDD; whether a hypothalamic defect is also involved in the altered regulation of LH secretion was not resolved. The compensatory increases in pituitary GnRH receptor number and plasma LH concentration elicited by low plasma testosterone concentrations were inhibited by similar doses of TCDD (ED50 20 micrograms TCDD/kg for both responses). We concluded that TCDD increases the potency of androgens as feedback inhibitors of LH secretion by increasing their potency as regulators of both pituitary GnRH receptor number and GnRH responsiveness. This is the first demonstration that TCDD treatment (i) affects pituitary responsiveness to a hormone secreted by a peripheral organ (testosterone), and (ii) alters the regulation of pituitary responsiveness to a hypothalamic hormone (GnRH).     

赛庚啶对大鼠下丘脑-腺垂体-性腺轴和钙调蛋白基因表达的影响(英文)

目的　研究赛庚啶 (Cyp)对SD大鼠生殖系统内分泌功能的影响是否有性别差异。方法　 60只SD大鼠依性别各分为 3组 ,每组 1 0只 ;分别灌胃给予生理盐水 ( 5mL·kg-1·d-1) ,Cyp( 2 .4,4.8mg·kg-1·d-1) ,共 1 4d或 2 1d。放免法测定血清黄体生成素 (LH)、促卵泡激素 (FSH)、雌二醇 (E2 )、孕酮(P)、睾酮 (T)的含量。光电镜观察促性腺激素释放激素细胞、促性腺激素细胞、间质细胞、支持细胞、黄体细胞、颗粒细胞等显微、超微结构的变化。用实时荧光定量PCR技术进行逆转录聚合酶链反应 ,琼脂糖凝胶电泳鉴定扩增产物。结果　Cyp可升高雄性大鼠血清LH、T的含量 ,而对FSH含量无明显影响。Cyp可升高雌性大鼠血清LH的水平 ,降低其FSH ,P ,E2 的含量。电镜发现 ,Cyp促进雄性大鼠分泌功能 ,使雌性大鼠内分泌细胞发生退行性改变。结论Cyp对雌性大鼠下丘脑 腺垂体 卵巢轴内分泌功能有抑制作用 ,而对雄性大鼠下丘脑 腺垂体 睾丸轴内分泌功能有促进作用 ,且使终末靶腺的内分泌细胞超微结构出现相应的变化。Cyp促进雄性大鼠睾丸钙调蛋白mRNA的表达可能与Cyp促进下丘脑 垂体 睾丸轴的内分泌功能有关     

Strain-dependency of procarbazine-induced testicular toxicity

Three strains of rat were used to examine strain-dependency of procarbazine-induced testicular toxicity. CCFHB and CCFY1 outbred albino rats and inbred PVG piebald variegated rats were treated weekly with procarbazine (200 mg/kg/dose x 4). Fifty-six days later, the rats were killed and reproductive parameters evaluated. Strain-related differences in body, testis, prostate, seminal vesicle weights, testis sperm, intratesticular testosterone, and [125I]hCG binding to testicular LH receptors were observed. Although treatment with procarbazine affected testis function in all strains, significant interactions occurred between treatment and strain. LH receptor binding and stem-cell survival were more severely affected in the inbred strain than in outbred strains. Serum testosterone increased in the outbred strain but decreased in the inbred strain, generating an interaction that obscured possible main effects. Significant strain-related differences in within-group variances demonstrated that measurements were more variable in the outbred strains than in the inbred strain. Testes of the inbred strain appeared to be more sensitive to the effects of procarbazine than those of the outbred strains. These data illustrate two important toxicologic phenomena: differences in response variability and differences in target-organ sensitivity, both of which were explained by genetic variability.     

Effects of heat-induced food contaminant furan on reproductive system of male rats from weaning through postpuberty

Furan (C₄H₄O) is a volatile, colorless liquid and is used in some segments of the chemical manufacturing industry. It is found in variety of foods such as coffee, jarred and canned foods that undergo heat treatment. This study was designed to investigate the effect of furan exposure on reproductive system of male rats. Three to four weeks old rats were exposed to furan at 2, 4 and 8 mg/kg/day doses by orally for 90 days. Hematology, weights, histology and morphometry of reproductive organs, serum LH and testosterone levels, sperm count and morphology and apoptosis in testis were evaluated. Slight changes were observed in hematological parameters of furan-treated rats. The weights of seminal vesicle reduced significantly whereas the weights of prostate increased significantly in the highest furan dose group. LH and testosterone levels decreased in furan-treated rats. Histological examinations have revealed that furan caused impairments in testis, epididymis and prostate gland. Furan showed no effects on sperm counts and morphology. On the other hand apoptotic cells in testis increased significantly. According to morphometrical examination, the epithelial heights and lumen diameters of the reproductive organs have changed in treatment groups. These results indicate that subchronic furan treatment induces toxicity of the male reproductive system.     

Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats.

3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats.     

Impairment of testicular endocrine function after lead intoxication in the adult rat

To clarify the mechanism of the action of lead on male reproductive function, adult male rats were injected intraperitoneally (i.p.) with lead acetate (8 mg/kg/day of lead), 5 days a week for 35 days. Despite this high dose, germ cells and Sertoli cells did not appear to be major targets of lead. However, lead determination in the reproductive organs showed that the accessory sex glands are such a target. Epididymal function was unchanged. In lead-exposed rats, plasma and testicular testosterone dropped by about 80%, but plasma luteinizing hormone (LH) only dropped by 32%. After luteinizing hormone releasing hormone (LHRH) stimulation of the pituitary, the plasma LH level reached the control one, but plasma testosterone remained significantly reduced by 37%. The sharp decrease in the testosterone: LH ratio in lead-exposed rats, combined with the significant reduction of intertubular tissue volume in the testes, indicate impaired Leydig cell function.