Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons.
Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons.
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DOI：
10.1371/journal.pone.0062776
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Oka Y
中科院分区：
文献类型：
--
作者：
Kanda S;Akazome Y;Mitani Y;Okubo K;Oka Y
神经肽Kispeptin被认为是生殖的重要中枢调节因子，以应对血清性激素浓度的变化。然而，尽管Kispeptin受体在大脑中广泛分布，尤其是在视前区和下丘脑，但研究的焦点大多局限于Kispeptin对GnRH神经元的调节。在这里，我们以已经被明确证明受性类固醇调节的Kispeptin(Kiss1)神经元的青竹为例，分析了Kisspeptin受体GPR54-1和GPR54-2的解剖分布。由于这两种受体都被Kisspeptins(Kiss1和Kiss2)激活，我们用原位杂交的方法分析了这两种受体的解剖分布。它们主要在腹侧端脑、视前区和下丘脑表达，被认为参与了包括生殖在内的动态平衡功能。首先，我们发现GPR54-2mRNA在大细胞部视前核中表达，并通过双重原位杂交证实了血管催产素和异催产素(分别为加压素和催产素直系物)神经元表达GPR54-2。考虑到Kispeptin的应用增加了哺乳动物的血清催产素和加压素浓度，目前的发现很可能是整个脊椎动物的现象，尽管尚未在哺乳动物中证明直接调节。然后，我们分析了Kispeptin受体在三种类型的GnRH神经元中的共表达。结果表明，尽管GnRH1神经元本身不是GnRH1神经元，但表达GPR54的细胞与GnRH1神经元相邻。而神经调节性GnRH2或GnRH3神经元周围无GPR54表达细胞。根据这些结果，我们认为青竹蛋白神经元通过血管催产素/异催产素神经元直接调节某些行为和神经内分泌功能，而它们至少不以直接方式调节促垂体素GnRH1神经元。因此，在哺乳动物中提出的对GnRH1神经元的直接Kisspeptin调节可能不是脊椎动物Kisspeptin系统的普遍特征。
Neuropeptide kisspeptin has been suggested to be an essential central regulator of reproduction in response to changes in serum gonadal steroid concentrations. However, in spite of wide kisspeptin receptor distribution in the brain, especially in the preoptic area and hypothalamus, the research focus has mostly been confined to the kisspeptin regulation on GnRH neurons. Here, by using medaka whose kisspeptin (kiss1) neurons have been clearly demonstrated to be regulated by sex steroids, we analyzed the anatomical distribution of kisspeptin receptors Gpr54-1 and Gpr54-2. Because the both receptors were shown to be activated by kisspeptins (Kiss1 and Kiss2), we analyzed the anatomical distribution of the both receptors by in situ hybridization. They were mainly expressed in the ventral telencephalon, preoptic area, and hypothalamus, which have been suggested to be involved in homeostatic functions including reproduction. First, we found gpr54-2 mRNA expression in nucleus preopticus pars magnocellularis and demonstrated that vasotocin and isotocin (Vasopressin and Oxytocin ortholog, respectively) neurons express gpr54-2 by dual in situ hybridization. Given that kisspeptin administration increases serum oxytocin and vasopressin concentration in mammals, the present finding are likely to be vertebrate-wide phenomenon, although direct regulation has not yet been demonstrated in mammals. We then analyzed co-expression of kisspeptin receptors in three types of GnRH neurons. It was clearly demonstrated that gpr54-expressing cells were located adjacent to GnRH1 neurons, although they were not GnRH1 neurons themselves. In contrast, there was no gpr54-expressing cell in the vicinities of neuromodulatory GnRH2 or GnRH3 neurons. From these results, we suggest that medaka kisspeptin neurons directly regulate some behavioral and neuroendocrine functions via vasotocin/isotocin neurons, whereas they do not regulate hypophysiotropic GnRH1 neurons at least in a direct manner. Thus, direct kisspeptin regulation of GnRH1 neurons proposed in mammals may not be the universal feature of vertebrate kisspeptin system in general.
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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：
2.7
作者：
Kanda, Shinji;Okubo, Kataaki;Oka, Yoshitaka
通讯作者：
Oka, Yoshitaka
影响因子：
4.1
作者：
Felip, Alicia;Zanuy, Silvia;Gomez, Ana
通讯作者：
Gomez, Ana
影响因子：
4.8
作者：
Kanda, Shinji;Akazome, Yasuhisa;Oka, Yoshitaka
通讯作者：
Oka, Yoshitaka
影响因子：
4.8
作者：
Kauffman, Alexander S.;Bojkowska, Karolina;Rissman, Emilie F.
通讯作者：
Rissman, Emilie F.