Endogenous kisspeptin tone is a critical excitatory component of spontaneous GnRH activity and the GnRH response to NPY and CART.
Endogenous kisspeptin tone is a critical excitatory component of spontaneous GnRH activity and the GnRH response to NPY and CART.
复制标题
DOI：
10.1159/000365419
复制
发表时间：
2014
影响因子：
4.1
通讯作者：
Smith MS
中科院分区：
文献类型：
--
作者：
Verma S;Kirigiti MA;Millar RP;Grove KL;Smith MS
Kisspeptin是GnRH神经元的主要兴奋性调节剂，负责基础GnRH/LH释放和GnRH/LH峰。尽管基于kisspeptin和Kiss 1 R的突变，人们普遍认为kisspeptin可以维持基础GnRH神经元的活性，但目前还没有研究调查内源性基础kisspeptin张力是否在基础自发GnRH神经元兴奋性中起直接作用。研究内源性kisspeptin张力与其他对GnRH神经元有直接影响的神经肽（如NPY或CART）之间可能的相互作用也很有意义，因为所有这些神经肽的活性在负能量平衡状态下都会发生变化。从雌性和雄性大鼠下丘脑切片中的GnRH-GFP神经元进行松散细胞贴附和全细胞电流钳膜片钳记录。Kisspeptin以浓度依赖性方式激活GnRH神经元，EC 50为3.32 ± 0.02 nM。令人惊讶的是，kisspeptin拮抗剂，肽347，抑制GnRH神经元的自发活动，证明了内源性kisspeptin音调的本质。此外，内源性kisspeptin张力的抑制阻断了响应于NPY Y 5 R或CART的拮抗作用而发生的GnRH细胞的直接激活。我们的电生理学研究表明，基础内源性kisspeptin紧张不仅是必不可少的自发性GnRH神经元放电，但它也需要其他神经肽，如CART或NPY拮抗剂，对GnRH神经元的净兴奋作用。因此，内源性kisspeptin张力可能是GnRH激活或抑制的关键。
Kisspeptin is the major excitatory regulator of GnRH neurons and is responsible for basal GnRH/LH release and the GnRH/LH surge. Although it is widely assumed, based on mutations in kisspeptin and Kiss1R, that kisspeptin acts to sustain basal GnRH neuronal activity, there have been no studies to investigate whether endogenous basal kisspeptin tone plays a direct role in basal spontaneous GnRH neuronal excitability. It is also of interest to examine possible interactions between endogenous kisspeptin tone and other neuropeptides that have direct effects on GnRH neurons, such as NPY or CART, since the activity of all these neuropeptides changes during states of negative energy balance. Loose cell-attached and whole cell current-clamp patch recordings were made from GnRH-GFP neurons in hypothalamic slices from female and male rats. Kisspeptin activated GnRH neurons in a concentration dependent manner with an EC50 of 3.32 ± 0.02 nM. Surprisingly, a kisspeptin antagonist, Peptide 347, suppressed spontaneous activity in GnRH neurons, demonstrating the essential nature of the endogenous kisspeptin tone. Furthermore, inhibition of endogenous kisspeptin tone blocked the direct activation of GnRH cells that occurs in response to antagonism of NPY Y5R or by CART. Our electrophysiology studies suggest that basal endogenous kisspeptin tone is not only essential for spontaneous GnRH neuronal firing, but it is also required for the net excitatory effects of other neuropeptides, such as CART or NPY antagonism, on GnRH neurons. Therefore, endogenous kisspeptin tone could serve as the linchpin in GnRH activation or inhibition.
登录
查看更多内容
影响因子：
4.8
作者：
de Croft, Simon;Piet, Richard;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
4.8
作者：
Guerriero, Kathryn A.;Keen, Kim L.;Terasawa, Ei
通讯作者：
Terasawa, Ei
影响因子：
4.8
作者：
Gottsch, ML;Cunningham, MJ;Steiner, RA
通讯作者：
Steiner, RA
影响因子：
3.2
作者：
Centeno, M.-L.;Sanchez, R. L.;Bethea, C. L.
通讯作者：
Bethea, C. L.