Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
Endocrinology. 2010 May;151(5):2233-43. doi: 10.1210/en.2009-1190. Epub 2010 Mar 5.
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 microg/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 microg/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.
Kisspeptin 刺激生殖，弓状核（ARC）中的 kisspeptin 细胞在小鼠中表达 Ob-Rb。在此，我们报告了在绵羊中的研究，以确定 kisspeptin 细胞是否表达 Ob-Rb 并对瘦素作出反应，以及 kisspeptin 细胞与 proopiomelanocortin（POMC）或神经肽 Y（NPY）细胞之间是否存在相互联系，以调节生殖和代谢功能。通过原位杂交测量去卵巢绵羊的 Kiss1 mRNA，这些绵羊体重正常、消瘦或消瘦并接受瘦素治疗（通过脑室内（icv）输注，4 μg/h，3 d）。促性腺激素释放不足的消瘦动物的 ARC 和视前区的 Kiss1 表达低于体重正常的动物，瘦素的 icv 输注部分恢复了消瘦动物的 Kiss1 表达。单细胞激光捕获显微切割与实时 PCR 相结合显示，视前区和 ARC 的 Kiss1 细胞表达 Ob-Rb。双荧光免疫组织化学显示 kisspeptin 细胞与 NPY 和 POMC 细胞之间存在相互联系。因此，我们用 kisspeptin（5 μg/h，icv）或载体处理去卵巢绵羊 20 h，并通过原位杂交检查 POMC 和 NPY 基因表达。Kisspeptin 处理减少了 POMC 并增加了 NPY 基因表达。因此，kisspeptin 神经元对瘦素作出反应，并且 Kiss1 mRNA 的表达受瘦素状态的影响。kisspeptin 细胞与 NPY 和 POMC 细胞相互通讯，改变靶细胞中相关基因的表达；相互联系也存在。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。
