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J Cell Biol:迟发性性腺机能减退症致病机理

2018-04-09 佚名 中科院动物所

男性也有“更年期”?是的。什么?你没听错,这就是迟发性性腺功能减退症,其特征为随年龄增长男性血液睾酮水平过度降低,同时伴有性功能障碍、体脂含量增加、肌肉容积和力量下降、骨密度降低、骨质疏松、记忆力和认知能力减退、情绪抑郁等一系列症状,最终可能导致多个器官或系统的功能异常,严重影响中老年男性健康。这一症状早在上个世纪的30年代就被发现和报道,一度被认为是一种正常的衰老伴随症状,直到2002年才被正式

男性也有“更年期”?是的。什么?你没听错,这就是迟发性性腺功能减退症,其特征为随年龄增长男性血液睾酮水平过度降低,同时伴有性功能障碍、体脂含量增加、肌肉容积和力量下降、骨密度降低、骨质疏松、记忆力和认知能力减退、情绪抑郁等一系列症状,最终可能导致多个器官或系统的功能异常,严重影响中老年男性健康。这一症状早在上个世纪的30年代就被发现和报道,一度被认为是一种正常的衰老伴随症状,直到2002年才被正式命名。这也导致人们对于男性迟发性性腺功能减退症的发病机制知之甚少。

近期中国科学院动物研究所研究员李卫带领的研究团队发现睾酮水平的下降与患者睾丸间质细胞中自噬水平的降低密切相关。睾酮主要在睾丸间质细胞中以胆固醇为原料合成,而此前有报道自噬参与在脂类的代谢当中,因而他们推测自噬可能主要通过调节脂类的代谢参与雄激素和合成。于是他们构建了在丸间质细胞中特异性敲除自噬相关基因Atg5和Atg7的小鼠模型,结果发现睾丸间质细胞中自噬的阻断能够引起小鼠血液睾酮浓度显着降低,进而导致小鼠交配行为、频率以及持续时间等性行为明显降低,其表型与男性迟发性性腺功能减退症非常类似。但是令人惊讶的是他们发现与此前的推测恰恰相反,睾丸间质细胞中特异性敲除自噬相关基因以后细胞内的脂类非但没有累积反而大量减少。进一步研究结果表明,细胞内脂蛋白受体SR-BI的一种负调控蛋白NHERF2的降解受到抑制,导致细胞内SR-BI的蛋白水平降低,阻碍了细胞对胆固醇的吸收,最终引起间质细胞中的睾酮合成减少。这些结果表明自噬除了参与细胞内脂类的消耗之外还参与了胆固醇等的吸收,睾丸间质细胞中自噬的阻断导致雄激素合成原料胆固醇吸收的障碍,进而导致雄激素合成不足,而自噬的功能异常可能是导致迟发性性腺机能减退症发生的重要原因。这项研究不但揭示了男性迟发性性腺功能减退症的致病新机制,同时也为该疾病的诊治提供了新的思路。

该项研究工作以Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells为题于4月4日在线发表于Journal of Cell Biology。该研究受到国家自然科学基金重大研究计划(91649202)、中科院先导专项(No.XDA16020701)和科技部“国家重点研发计划”重点专项(2016YFA0500901)的资助。

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    2019-02-04 sunylz
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1918018, encodeId=aa72191801870, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Feb 04 14:51:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2010670, encodeId=516d20106e039, content=<a href='/topic/show?id=ce9086483c8' target=_blank style='color:#2F92EE;'>#致病机理#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86483, encryptionId=ce9086483c8, topicName=致病机理)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=649f191, createdName=zzc2211, createdTime=Sat Nov 24 14:51:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870549, encodeId=9cbb18e0549b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Jun 06 21:51:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767414, encodeId=4d121e67414a7, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Thu Aug 09 23:51:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034408, encodeId=db672034408f1, content=<a href='/topic/show?id=45eb94588cd' target=_blank style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Wed Dec 19 00:51:00 CST 2018, time=2018-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960817, encodeId=7a74196081ed9, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Jul 11 20:51:00 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304295, encodeId=c93b30429559, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 09 22:44:40 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304291, encodeId=82b83042911e, content=不错的文章值得拥有的, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Apr 09 22:32:24 CST 2018, time=2018-04-09, status=1, ipAttribution=)]
    2018-07-11 维他命
  7. [GetPortalCommentsPageByObjectIdResponse(id=1918018, encodeId=aa72191801870, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Feb 04 14:51:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2010670, encodeId=516d20106e039, content=<a href='/topic/show?id=ce9086483c8' target=_blank style='color:#2F92EE;'>#致病机理#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86483, encryptionId=ce9086483c8, topicName=致病机理)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=649f191, createdName=zzc2211, createdTime=Sat Nov 24 14:51:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870549, encodeId=9cbb18e0549b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Jun 06 21:51:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767414, encodeId=4d121e67414a7, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Thu Aug 09 23:51:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034408, encodeId=db672034408f1, content=<a href='/topic/show?id=45eb94588cd' target=_blank style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Wed Dec 19 00:51:00 CST 2018, time=2018-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960817, encodeId=7a74196081ed9, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Jul 11 20:51:00 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304295, encodeId=c93b30429559, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 09 22:44:40 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304291, encodeId=82b83042911e, content=不错的文章值得拥有的, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Apr 09 22:32:24 CST 2018, time=2018-04-09, status=1, ipAttribution=)]
    2018-04-09 131****2916

    不错的文章值得推荐

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1918018, encodeId=aa72191801870, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Feb 04 14:51:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2010670, encodeId=516d20106e039, content=<a href='/topic/show?id=ce9086483c8' target=_blank style='color:#2F92EE;'>#致病机理#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86483, encryptionId=ce9086483c8, topicName=致病机理)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=649f191, createdName=zzc2211, createdTime=Sat Nov 24 14:51:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870549, encodeId=9cbb18e0549b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Jun 06 21:51:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767414, encodeId=4d121e67414a7, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Thu Aug 09 23:51:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034408, encodeId=db672034408f1, content=<a href='/topic/show?id=45eb94588cd' target=_blank style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Wed Dec 19 00:51:00 CST 2018, time=2018-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960817, encodeId=7a74196081ed9, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Jul 11 20:51:00 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304295, encodeId=c93b30429559, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 09 22:44:40 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=304291, encodeId=82b83042911e, content=不错的文章值得拥有的, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Apr 09 22:32:24 CST 2018, time=2018-04-09, status=1, ipAttribution=)]
    2018-04-09 1e1b8538m79(暂无匿称)

    不错的文章值得拥有的

    0

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