雌性小鼠下丘脑生殖功能相关基因mRNA表达水平的增龄性变化  

Profiles of reproduction-related mRNA expressions in hypothalamus of female mice with advancing age

作　　者：张静 杨璐萌 潘晓东[2] 陈晓春[2] 

机构地区：[1]福建省高校脑老化与神经变性疾病重点实验室,福建省老年医学研究所,福州350001 [2]福建省分子神经病学重点实验室,福建医科大学附属协和医院神经内科

出　　处：《中华医学杂志》2013年第47期3791-3795,共5页National Medical Journal of China

基　　金：国家“973”重点基础研究发展计划项目（2007CB507404）;福建省教育厅科技项目（JK2010025）

摘　　要：目的探讨增龄对下丘脑生殖功能相关基因-Gnrh、KISS1／KISS1r、ERa、ER13及PRmRNA表达水平的影响。方法以年轻、中年和老年的雌性小鼠为对象，依据动情周期将其分为动情前期和动情后期组（动情间期第一天），老年鼠取动情间期组。解剖分离下丘脑前部视前区（POA—AH）和基底下丘脑（MBH），通过实时RT-PCR方法检测相关基因的mRNA水平。结果中年鼠动情前期GnrhmRNA水平（0．896±0．049）明显低于年轻鼠（1．228±0．147，P=0．049）。年轻鼠动情前期POA．AH内ERamRNA水平较动情后期明显下降，中年鼠动情前期（0．603±0．018）较动情后期（0．432±0．063，P=0．016）不仅未下降、反而升高，中年鼠（0．432±0．063，P=0．014）和老年鼠（0．403±0．145，P=0．020）动情间期POA—AH内ERamRNA水平均低于年轻鼠。中年鼠动情前期PRmRNA水平（1．037±0．037）明显低于年轻鼠（1．251±0．081，P=0．031）。老年鼠POA—AH内GnrhmRNA（1．520±0．146，P=0．004）和ER13mRNA（1．572±0．184，P=0．011）水平均高于年轻鼠动情后期。增龄不影响POA—AH内KISS1和KISS1r的mRNA水平，但中年鼠（1．663±0．398，P=0．037）和老年鼠（2．622±0．454，P=0．014）动情间期MBH内KISS1的mRNA水平明显高于年轻鼠。结论中年鼠动情前期时POA．AH内ERamRNA水平的增加、PR和GnrhmRNA水平的下降可能在生殖功能衰退的早期阶段发挥重要的作用。[ Abstract] Objective To explore the effects of aging on the levels of reproduction-related mRNA genes including Gnrh, KISS1/KISS1 r, estrogen receptor-alpha （ERa）, estrogen receptor-beta （ERI3） and progesterone receptor （PR） in hypothalamus. Methods Proestrus and metestrus in young （3 -4 months） and middle-aged （10- 11 months） female mice and diestms in senile （18 -19 months） female mice were observed. And the levels of related mRNA genes in preoptic area anterior hypothalamus （POA-AH） and medial basal hypothalamus （MBH） were determined by real-time polymerase chain reaction （RT-PCR）. Results In middle-aged mice on proestrus, the level of Gnrh mRNA in POA-AH （0. 896 _± 0. 049） was significantly lower than that in young mice （1. 228 ±0. 147, P =0. 049）. The level of ERa mRNA in POA- AH decreased in young mice on proestms whereas increased in middle-aged mice （0. 432 ± 0. 063 vs 0. 603 ±0. 018, P =0. 016）. The level of ERc± mRNA of POA-AH, both in middle-aged mice （0. 432 ± 0. 063, P =0. 014） and senile mice （0. 403 -±0. 145, P =0. 020） on diestrus, were significantly lower than that in young mice. The PR mRNA expression in middle-aged mice on proestrus （ 1. 037 ± 0. 037 ） was markedly lower than that in young mice（ 1. 251 _± 0. 081, P = 0. 031 ）. In senile mice, the levels of Gnrh mRNA （ 1. 520 ± 0. 146, P = 0. 004） and ER± mRNA （ 1. 572 ± 0. 184, P = 0. 011 ） increased in POA-AH compared with that in young mice on metestrus. Aging had no effect upon KISS1 and KISSlr mRNA levels in POA-AH. In contrast, KISS1 mRNA level of MBH in middle-aged （1. 663 ±0. 398, P =0. 037） and senile （2. 622 ±0. 454, P = 0. 014） mice obviously increased compared with the young mice group. ConclusionHigher levels of ERc~ mRNA and decreases of PR and Gnrh mRNA in POA-AH in middle-aged mice on proestrus may play an important role in declining reproductive function.

关 键 词：老化 GnRH神经元 雌激素受体 孕酮受体 KISS1 

分 类 号：R285.5[医药卫生—中药学]