Kisspeptin Cells in the Ewe Brain Respond to Leptin and Communicate with Neuropeptide Y and Proopiomelanocortin Cells

Kisspeptin Cells in the Ewe Brain Respond to Leptin and Communicate with Neuropeptide Y and Proopiomelanocortin Cells
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DOI:
10.1210/en.2009-1190
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发表时间:
2010-05-01
期刊:
影响因子:
4.8
通讯作者:
Clarke, Iain J.
Clarke, Iain J.
中科院分区:
医学2区
文献类型:
--
作者:
Backholer, Kathryn;Smith, Jeremy T.;Clarke, Iain J.

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Kisspeptin刺激生殖,弓状核(ARC)中的Kisspeptin细胞在小鼠中表达Ob-Rb。在此,我们报告的研究在母羊,以确定是否kisspeptin细胞表达Ob-Rb和响应瘦素和kisspeptin细胞和阿黑皮素原(POMC)或神经肽Y(NPY)细胞之间是否存在相互连接,以调节生殖和代谢功能。Kiss 1 mRNA的原位杂交测定卵巢切除母羊是正常体重,瘦,瘦与瘦治疗脑室内(icv)输液(4 μ g/h,3天)。Kiss 1在ARC和视前区的表达是低促性腺激素瘦动物比正常体重的动物,和icv输注瘦素部分恢复Kiss 1在瘦动物的表达。单细胞激光捕获显微切割结合实时荧光定量PCR显示,Kiss 1细胞在视前区和ARC表达Ob-Rb。双标记荧光免疫组化显示,kisspeptin细胞与NPY和POMC细胞之间存在相互联系。因此,我们用kisspeptin(5 μ g/h,icv)或溶剂处理卵巢切除母羊20小时,并通过原位杂交检测POMC和NPY基因表达。Kisspeptin治疗减少POMC和增加NPY基因表达。因此,kisspeptin神经元响应瘦素和Kiss 1 mRNA的表达受瘦素状态的影响。Kisspeptin细胞与NPY和POMC细胞通讯,改变靶细胞中相关基因的表达;也存在相互连接。这三种细胞类型之间的网络可以协调大脑对生殖和代谢稳态系统的控制。(内分泌学151:2233-2243,2010)
Kisspeptin stimulates reproduction, and kisspeptin cells in the arcuate nucleus (ARC) express Ob-Rb in the mouse. Herein we report studies in ewes to determine whether kisspeptin cells express Ob-Rb and respond to leptin and whether reciprocal connections exist between kisspeptin cells and proopiomelanocortin (POMC) or neuropeptide Y (NPY) cells to modulate reproduction and metabolic function. Kiss1 mRNA was measured by in situ hybridization in ovariectomized ewes that were normal body weight, lean, or lean with leptin treatment by intracerebroventricular (icv) infusion (4 mu g/h, 3 d). Kiss1 expression in the ARC and the preoptic area was lower in hypogonadotropic lean animals than animals of normal weight, and icv infusion of leptin partially restored Kiss1 expression in lean animals. Single-cell laser capture microdissection coupled with real-time PCR showed that Kiss1 cells in the preoptic area and ARC express Ob-Rb. Double-label fluorescent immunohistochemistry showed that reciprocal connections exist between kisspeptin cells and NPY and POMC cells. Accordingly, we treated ovariectomized ewes with kisspeptin (5 mu g/h, icv) or vehicle for 20 h and examined POMC and NPY gene expression by in situ hybridization. Kisspeptin treatment reduced POMC and increased NPY gene expression. Thus, kisspeptin neurons respond to leptin and expression of Kiss1 mRNA is affected by leptin status. Kisspeptin cells communicate with NPY and POMC cells, altering expression of the relevant genes in the target cells; reciprocal connections also exist. This network between the three cell types could coordinate brain control of reproduction and metabolic homeostatic systems. (Endocrinology 151: 2233-2243, 2010)