Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes.
Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes.
复制标题
DOI：
10.1111/jne.12163
复制
发表时间：
2014-07
影响因子：
3.2
通讯作者：
Acosta-Martínez M
中科院分区：
文献类型：
--
作者：
Aziz R;Beymer M;Negrón AL;Newshan A;Yu G;Rosati B;McKinnon D;Fukuda M;Lin RZ;Mayer C;Boehm U;Acosta-Martínez M
甘丙肽样肽（GALP）神经元参与生殖的代谢控制，是胰岛素和瘦素调节的靶点。磷脂酰肌醇3-激酶（PI3K）是胰岛素和瘦素共同利用的信号通路。因此，我们研究了表达GALP的神经元中的PI3K信号传导是否在GALP基因的转录调控和促黄体生成素（LH）释放的代谢控制中起作用。为此，我们在小鼠中通过条件基因靶向（cKO）（GALP-p110 α/β cKO）删除PI3K催化亚基p110 α和p110 β。为了监测GALP神经元中的PI3K信号传导，还将这些动物与Cre依赖性FoxO1GFP报告小鼠杂交。与胰岛素输注的对照动物相比，GALP-p110 α/β cKO小鼠中GALP神经元中的PI3K-Akt依赖性FoxO1GFP核排斥被消除。接下来，我们使用食物剥夺来研究PI3K活性的GALP神经元特异性消融是否影响促性腺轴对负能量平衡的易感性。给药未影响两种性别的LH水平。然而，在女性中观察到LH水平的显着基因型效应。相反，在男性中未观察到基因型对LH水平的影响。观察到性别特异性基因型对下丘脑GALP mRNA的影响，进食和禁食GALP-p110 α/β cKO雄性动物的GALP mRNA表达低于WT进食雄性动物。最后，研究了性腺切除和类固醇激素替代对GALP mRNA水平的影响。与溶剂处理的小鼠相比，类固醇激素替代减少了WT和GALP-p110 α/β cKO动物中的MBH GALP表达。此外，在去势和溶剂给药组内，与WT相比，GALP-p110 α/β cKO雄性动物的LH水平较低。使用GALP-Cre/R26-YFP小鼠的双重免疫荧光显示GALP神经元内的雄激素和雌激素受体共定位。我们的数据表明，GALP神经元是类固醇激素的直接靶点，PI3K信号以性别特异性方式调节下丘脑GALP mRNA表达和LH水平。
Galanin-like peptide (GALP) neurons participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signaling pathways utilized by both insulin and leptin. Therefore, we investigated whether PI3K signaling in neurons expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinizing hormone (LH) release. To this end, we deleted PI3K catalytic subunits, p110α and p110β via conditional gene targeting (cKO) in mice (GALP-p110α/β cKO). To monitor PI3K signaling in GALP neurons these animals were also crossed with Cre-dependent FoxO1GFP reporter mice. Compared to insulin-infused control animals, the PI3K-Akt-dependent FoxO1GFP nuclear exclusion in GALP neurons was abolished in GALP-p110α/β cKO mice. We next used food deprivation to investigate if the GALP-neuron specific ablation of PI3K activity affected the susceptibility of the gonadotropic axis to negative energy balance. Treatment did not affect LH levels in either sex. However, a significant genotype effect on LH levels was observed in females. In contrast, no genotype effect on LH levels was observed in males. A sex-specific genotype effect on hypothalamic GALP mRNA was observed, with fed and fasted GALP-p110α/β cKO males having lower GALP mRNA expression compared to WT fed males. Finally, the effects of gonadectomy and steroid hormone replacement on GALP mRNA levels were investigated. Compared to vehicle-treated mice, steroid hormone replacement reduced MBH GALP expression in WT and GALP-p110α/β cKO animals. In addition, within the castrated and vehicle-treated group and compared to WT, LH levels were lower in GALP-p110α/β cKO males. Double immunofluorescence using GALP-Cre/R26-YFP mice showed androgen and estrogen receptor co-localization within GALP neurons. Our data demonstrate that GALP neurons are direct targets of steroid hormones and that PI3K signaling regulates hypothalamic GALP mRNA expression and LH levels in a sex-specific fashion.
登录
查看更多内容
影响因子：
7.4
作者：
Lawrence, Catherine;Fraley, Gregory S.
通讯作者：
Fraley, Gregory S.
影响因子：
29
作者：
Al-Qassab H;Smith MA;Irvine EE;Guillermet-Guibert J;Claret M;Choudhury AI;Selman C;Piipari K;Clements M;Lingard S;Chandarana K;Bell JD;Barsh GS;Smith AJ;Batterham RL;Ashford ML;Vanhaesebroeck B;Withers DJ
通讯作者：
Withers DJ
影响因子：
3.5
作者：
Kauffman, AS;Buenzle, J;Rissman, EF
通讯作者：
Rissman, EF
影响因子：
5.3
作者：
Fukuda, Makoto;Jones, Juli E.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.
影响因子：
6.9
作者：
Golde, WT;Gollobin, P;Rodriguez, LL
通讯作者：
Rodriguez, LL