关于抑制素的回顾与展望

1923年,随着生殖腺反馈调节垂体功能的概念的提出,关于抑制素的研究开始了。抑制素是一种非类固醇类物质,能够抑制垂体细胞的活性。1932年,这种物质在水状的睾丸提取物中得到证实,并被命名为抑制素。又经过了50多年的研究,到1985年,抑制素才被纯化和克隆。而直到化验技术的进步使人和动物的循环浓度得以分析,抑制素的生理活性的揭示才得以完成。本文综述抑制素的历史、生理作用及其在辅助生殖技术中的最新的应用和研究。     

Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

2型糖尿病患者绝经期骨密度与甲状旁腺素、雌激素相关性研究

目的 观察2型糖尿病妇女绝经期骨密度与甲状旁腺素、雌激素相关性研究.方法 测定绝经期2型糖尿病妇女伴骨质疏松（A）组及绝经期2型糖尿病妇女无骨质疏松（B）组的左侧髋部股骨颈、大转子、华氏三角区、及腰椎L2～L4正侧位的骨密度和血清中骨代谢指标,如：骨钙素、碱性磷酸酶、钙、磷、甲状旁腺素、雌二醇、Ⅰ型胶原羧基末端终肽（β-CTx）的浓度,对骨密度与多个变量之间的关系进行相关分析,并对（A）组血清中的甲状旁腺素、雌二醇、骨钙素、β-CTx与不同部位的骨密度之间的关系进行多元逐步回归分析.结果绝经期2型糖尿病妇女（B）组的腰椎、大转子、华氏三角区、股骨颈等骨密度指标明显低于对照组（A）（P＜0.05）;2型糖尿病绝经期妇女血清中雌二醇水平与腰椎L2～L4骨密度呈正相关（P＜0.032）;甲状旁腺素水平与股骨颈骨密度呈负相关（P＜0.034）.结论 绝经期2型糖尿病患者甲状旁腺素和雌激素水平与骨密度密切相关,分别可以用于预测骨质疏松发生的不同部位.     

rhIL-1Ra对恒河猴肾脏毒性的病理组织学观察

目的 观察重组人白介素-1受体拮抗剂(rhIL-1Ra)的毒性靶器官及毒性的严重程度.方法 32只成年恒河猴分为rhIL-1Ra 2mg/(kg·d)(n=6)、10mg/(kg·d)(n=6)和50mg/(kg·d)(n=6)连续给药90天组,10mg/(kg·d)(n=4)连续给药30天组,正常对照组(n=5)和溶剂对照组(n=5).rhIL-1Ra为皮下注射给药,每日1次.观察指标包括一般药物反应、尿八项、心电图、眼底检查、外周血细胞计数及白细胞分类、凝血时间、血清生化、外周血T细胞亚群和猴抗rhIL-1Ra抗体测定、脏器重量和脏器系数、常规病理组织学检查.结果 给药后30天各给药组动物血清非特异性抗体明显升高.rhIL-1Ra 2mg/(kg·d)组其他检测指标均未见明显地改变.rhIL-1Ra 10mg/(kg·d)组给药后90天肾小球毛细血管基底膜明显增厚,但此剂量给药时间为30天时未见任何异常.rhIL-1Ra 50mg/(kg·d)组肾小球及肾小管中蛋白性液体量多,小球毛细血管基底膜增厚更为严重,且停药30天后基底膜增厚程度仍未见明显减轻或改善.结论 rhIL-1Ra的主要毒性靶器官为肾脏,2mg/(kg·d)为安全剂量,10mg/(kg·d)给药30天时为安全剂量,给药90天为恒河猴中毒性剂量,而50mg/(kg·d)为明显的毒性反应剂量,可产生难以恢复的肾脏纤维化.     

多巴胺受体与其他血压调节系统的交互作用在高血压研究中的地位

肾脏是人体负责钠排泄的重要器官,多巴胺由于其强大的抑制肾脏钠重吸收作用而在原发性高血压的发生、发展中发挥重要作用。多巴胺受体的5个亚型均直接或间接通过与其他血压调节系统的交互作用,参与肾脏钠通道或血压的调节。现就多巴胺受体在调节机体血压和肾脏利钠、利尿作用中所发挥的重要作用作一综述。     

Gonadotropins mediate DNA synthesis and protection from spontaneous cell death in human ovarian surface epithelium

Gonadotropins have been implicated in the development of epithelial ovarian cancers. These tumors are derived from ovarian surface epithelium (OSE). The purpose of this study was to determine the effects of these hormones on DNA synthesis and spontaneous cell death in primary cultures of OSE and three immortalized OSE cultures. Primary cultures of OSE cells were generated from the ovaries of women with benign disease. The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on DNA synthesis and cell death were determined using [(3)H]thymidine incorporation and JAM assays. Significant inductions of DNA synthesis were demonstrated with LH in 4/12 (33%) primary cultures of OSE and 2/3 OSE cell lines and with FSH in 4/11 (36%) primary cultures of OSE and 2/3 OSE cell lines. A significant protection from cell death was also observed in the presence of FSH in 2/4 primary cultures of OSE and 1/3 OSE cell lines and in the presence of LH in 1/4 primary cultures of OSE and 2/3 OSE cell lines. The results indicate that while gonadotropins have the potential to induce cell proliferation and protect from cell death in OSE cells in vitro, their effects are variable in OSE cells from different women.     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.     

曲尼司特对豚鼠肺组织β肾上腺素受体向下调节的影响

用放射配体结合分析法分别测定了正常组、特布他林组、特布他林十曲尼司特组豚鼠的肺组织β受体最大结合力和解离常数,结果显示:给特布他林后豚鼠肺组织β受体发生明显的向下调节.曲尼司特可预防此向下调节的发生.     

The consequences of H2 receptor antagonist — piroxicam coadministration in patients with joint disorders

Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L^–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC_0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC_0-24(5-OHP)], the ratio of these i.e. AUC_0-24(5-OHP):AUC_0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC_0-23(5-OHP):AUC_0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.