中老龄雄性大鼠雄激素减低与代谢关系及发病机制的研究  

Serum testosterone reduction and metabolism in aging male rats: Correlation and mechanism

作　　者：关迪[1] 周芳[2,3] 葛争艳[4] 卢文红[2,3] 袁冬[2,3] 梁小薇[2,3] 周善杰[2,3] 李志广[1,2,3] 谷翊群[2,3] 

机构地区：[1]北京协和医学院研究生院,北京100730 [2]国家人口计生委科学技术研究所 [3]WHO人类生殖研究合作中心,北京100081 [4]中国中医科学院西苑医院男科,北京100091

出　　处：《中华男科学杂志》2011年第7期579-585,共7页National Journal of Andrology

基　　金：中央级公益性科研院所基本科研业务费专项(2009GJSSJKB02)~~

摘　　要：目的:研究中老龄雄性大鼠雄激素减低与代谢的关系,雄激素减低发生的机制,尤其是睾丸间质细胞数量、形态及分泌功能的变化。方法:分别取9月龄(中青龄)和12、15、18、21月龄(中老龄)雄性SD大鼠每月龄组6只,静脉血检测大鼠代谢指标的变化,包括高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、甘油三酯(TG)、总胆固醇(TC)、血糖(Glu)、胰岛素(INS)、胰高血糖素(IRG)、瘦素(LP)含量;检测大鼠血清激素的改变,包括总睾酮(tT)、黄体生成素(LH)、卵泡刺激素(FSH);通过组织切片观察大鼠睾丸间质细胞形态学变化;使用人绒毛膜促性腺激素(hCG)、毛喉素(Forskolin)刺激体外培养的大鼠睾丸间质细胞,比较培养液中睾酮(T)浓度;采用脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测大鼠睾丸间质细胞凋亡率;分离称重内脏脂肪,计算内脏脂肪/体重比及Lee's指数。结果:中老龄大鼠的血清tT[(1.26±0.65)ng/ml]比中青龄大鼠[(3.24±0.38)ng/ml]显著降低(P<0.01);中老龄大鼠睾酮分泌指数(TSI)[(0.07±0.05)ng/mIU]比中青龄大鼠[(0.21±0.01)ng/mIU]显著降低(P<0.01);不同年龄大鼠睾丸间质细胞形态有较显著差异;体外培养的中老龄大鼠睾丸间质细胞在24、48、72 h内T分泌量均显著低于中青龄大鼠(P<0.05);中老龄大鼠睾丸间质细胞TUNEL阳性率[(17.36±1.31)%]比中青龄大鼠[(7.02±1.05)%]显著升高(P<0.01);中老龄组和中青龄组大鼠IRG、HDL、LDL、TG、TC及内脏脂肪含量有显著性差异(P<0.05)。结论:中老龄大鼠血清tT浓度显著低于中青龄大鼠,代谢指标随血清tT降低发生规律改变;中老龄大鼠雄激素减低可能与睾丸间质细胞分泌功能衰退、间质细胞数量减少及垂体功能衰退有关。Objective： To investigate the mechanism of serum testosterone reduction, its relationship with metabolism, changes in the number and morphology of Leydig cells and endocrine function in aging male rats. Methods： The levels of serum total testosterone （tT）, LH, FSH, HDL, LDL, TG, TC, Glu, INS, IRG and LP were determined in young （9 mo） and aging rats （12, 15, 18 and 21 too）, with 6 in each group. The morphological changes of Leydig cells were observed under the microscope. The concentrations of testosterone secreted from the cultured Leydig cells with the stimulation of hCG and Forskolin were assayed. The apopto- sis rates of Leydig cells were detected by TUNEL. The visceral fat was isolated and weighed, and the Lee~ index calculated. All the a- bove indexes were recorded and compared among different age groups. Results： The aging rats showed a significant decrease in the levels of serum tT and TSI （ [ 1.26 ± 0.65 ] ng/ml and [ 0. 07 ± 0.65 ] ng/mlU） as compared with the young rats （ [ 3.24 ± 0.38 ng/ml and [ 0.21 ± 0. 01 ] ng/mIU） （P 〈 0. 01 ）. Obvious differences were found in the morphology of Leydig cells among different age groups. The T secretion of Leydig cells at 24, 48 and 72 h in aging rats was markedly decreased （P 〈 0.05 ） while their TUNEL positive rate remarkably increased in the aging rats （17.36% ± 1.31% ） compared with the young ones （7.02% ± 1.05% ） （P 〈 0.05）. There were statistically significant differences between the young and aging rats in all the biochemical parameters including IRG, HDL, LDL, TG, TC and visceral fat content （P 〈 0.05）, except the levels of serum Glu, INS and LP （P 〉 0.05）. Con- clusion ： The serum T level and secreting capacity of Leydig cells are significantly lower in aging rats than in young ones, and the meta- bolic parameters undergo regular changes with the decreasing level of serum T. The reduction of testosterone in aging male rats may be associated with the decreased secreting capacity and num

关 键 词：中老龄大鼠 代谢 间质细胞 睾酮 

分 类 号：R588[医药卫生—内分泌]