Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation.
Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation.
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DOI：
10.1530/rep-20-0447
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Narayan P
中科院分区：
文献类型：
--
作者：
Hiremath DS;Priviero FBM;Webb RC;Ko C;Narayan P
适时激活黄体生成素受体（LHCGR）对生育至关重要。LHCGR的激活突变导致家族性男性限制性性早熟（FMPP），这是由于睾酮的过早合成。我们的实验室先前开发了一种小鼠FMPP模型（KiLHRD582G），表达LHCGR中的组成性激活突变。KiLHRD582G小鼠由于性功能障碍而逐渐不育，并表现出阴茎平滑肌损失和软骨细胞积聚。在这项研究中，我们验证了KiLHRD582G小鼠由于平滑肌功能受损而出现勃起功能障碍的假设。阿波吗啡诱导的勃起研究表明，KiLHRD582G小鼠存在勃起功能障碍。用阴茎海绵体条评估阴茎平滑肌和内皮功能。KiLHRD582G小鼠阴茎内皮细胞含量未发生变化。KiLHRD582G小鼠对乙酰胆碱和一氧化氮供体硝普钠的最大松弛反应显著降低，表明一氧化氮（NO）介导的信号通路受损。乙酰胆碱、硝普钠和可溶性鸟苷环化酶刺激剂BAY 41-2272可显著降低KiLHRD582G小鼠的环鸟苷单磷酸（cGMP）水平。NOS1、NOS3和PKRG1的表达不变。平滑肌收缩的rho激酶信号通路没有改变。综上所述，这些数据表明，KiLHRD582G小鼠的勃起功能障碍是由于no介导的可溶性鸟苷酸环化酶激活受损，导致cGMP水平下降和阴茎平滑肌松弛。这些在KiLHRD582G小鼠中的研究表明，小鼠LHCGR的激活突变由于no介导的阴茎平滑肌信号通路的损伤而导致勃起功能障碍。
Timely activation of the luteinizing hormone receptor (LHCGR) is critical for fertility. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP) due to premature synthesis of testosterone. A mouse model of FMPP (KiLHRD582G), expressing a constitutively activating mutation in LHCGR, was previously developed in our laboratory. KiLHRD582G mice became progressively infertile due to sexual dysfunction and exhibited smooth muscle loss and chondrocyte accumulation in the penis. In this study we tested the hypothesis that KiLHRD582G mice had erectile dysfunction due to impaired smooth muscle function. Apomorphine-induced erection studies determined that KiLHRD582G mice had erectile dysfunction. Penile smooth muscle and endothelial function were assessed using penile cavernosal strips. Penile endothelial cell content was not changed in KiLHRD582G mice. The maximal relaxation response to acetylcholine and the nitric oxide donor, sodium nitroprusside, was significantly reduced in KiLHRD582G mice indicating an impairment in the nitric oxide (NO)- mediated signaling. Cyclic guanosine monophosphate (cGMP) levels were significantly reduced in KiLHRD582G mice in response to acetylcholine, sodium nitroprusside and the soluble guanylate cyclase stimulator, BAY 41-2272. Expression of NOS1, NOS3 and PKRG1 were unchanged. The Rho-kinase signaling pathway for smooth muscle contraction was not altered. Together, these data indicate that KiLHRD582G mice have erectile dysfunction due to impaired NO-mediated activation of soluble guanylate cyclase resulting in decreased levels of cGMP and penile smooth muscle relaxation. These studies in the KiLHRD582G mice demonstrate that activating mutations in the mouse LHCGR cause erectile dysfunction due to impairment of the NO-mediated signaling pathway in the penile smooth muscle.
DOI：
10.1016/j.bbrc.2009.01.144
发表时间：
2009-03-20
影响因子：
3.1
作者：
Yang, Rong;Huang, Yun-Ching;Lin, Guiting;Wang, Guifang;Hung, Steven;Dai, Yu-Tian;Sun, Ze-Yu;Lue, Tom F.;Lin, Ching-Shwun
通讯作者：
Lin, Ching-Shwun