Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin.
Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin.
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生长激素过度表达通过对瘦素的作用破坏生殖状态
DOI：
10.3389/fendo.2018.00131
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发表时间：
2018
影响因子：
5.2
通讯作者：
Hu W
中科院分区：
文献类型：
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作者：
Chen J;Cao M;Zhang A;Shi M;Tao B;Li Y;Wang Y;Zhu Z;Trudeau VL;Hu W
生长和繁殖密切相关。转生长激素基因鲤鱼的生长速度加快，生殖发育延迟，这为研究生长轴和生殖轴之间的激素串扰提供了一个可行的模型。采用多组织RNA测序、实时荧光定量PCR、Western blotting、ELISA、免疫荧光和体外培养等方法，对转GH基因鲤的能量状况和生殖发育进行了分析。转GH基因鲤鱼的糖原合成酶（gys）和胰岛素样生长因子结合蛋白（igfbp1）的表达以及血糖浓度均较低。与食欲和脂代谢相关的Agrp1和sla在转GH基因鲤鱼中显著升高。低葡萄糖含量和食欲增加表明GH转基因鲤鱼的代谢和能量剥夺状态中断。与此同时，GH转基因鲤鱼的基因表达减少，如垂体中的gnrhr 2（促性腺激素释放激素受体2）、gthα（促性腺激素，α多肽）、fshβ（促卵泡激素，β多肽）、lhβ（促黄体激素，β多肽）、性腺中的cyp19 a1 a（芳香酶A）和下丘脑中的cyp19 a1 B（芳香酶B）。与此相反，垂体gnih（促性腺激素抑制激素）、drd1（多巴胺受体D1）、drd3（多巴胺受体D3）和drd4（多巴胺受体D4）表现出表达增加，这与生殖发育迟缓有关。荧光原位杂交检测到瘦素受体mRNA在垂体，包括中间部和近端远侧部，表明瘦素对LH的直接影响。重组鲤鱼Leptin蛋白在体外刺激垂体GTHα、FSHβ、LHβ的表达和卵巢生殖囊泡破裂。除了神经内分泌因素，我们认为，减少肝脏瘦素信号的垂体可能是一部分的反应过度生长激素和由此导致的延迟青春期的开始。
Growth and reproduction are closely related. Growth hormone (GH)-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and in vitro incubation. The expression of gys (glycogen synthase) and igfbp1 (insulin-like growth factor binding protein) as well as blood glucose concentrations are lower in GH-transgenic carp. Agrp1 (agouti-related protein 1) and sla (somatolactin a), which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2), gthα (gonadotropin hormone, alpha polypeptide), fshβ (follicle stimulating hormone, beta polypeptide), lhβ [luteinizing hormone, beta polypeptide] in the pituitary, cyp19a1a (aromatase A) in the gonad, and cyp19a1b (aromatase B) in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih (gonadotropin inhibitory hormone), drd1 (dopamine receptor D1), drd3 (dopamine receptor D3), and drd4 (dopamine receptor D4) exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence in situ hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthα, fshβ, lhβ expression, and ovarian germinal vesicle breakdown in vitro. In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the pituitary might be part of the response to overexpression of GH and the resulting delay in puberty onset.