Gonadotropin-releasing hormone-II messenger ribonucleic acid and protein content in the mammalian brain are modulated by food intake

Gonadotropin-releasing hormone-II messenger ribonucleic acid and protein content in the mammalian brain are modulated by food intake
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DOI:
10.1210/en.2006-0615
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发表时间:
2006-11-01
期刊:
影响因子:
4.8
通讯作者:
Rissman, Emilie F.
Rissman, Emilie F.
中科院分区:
医学2区
文献类型:
--
作者:
Kauffman, Alexander S.;Bojkowska, Karolina;Rissman, Emilie F.

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GnRH- ii是GnRH肽家族中进化上最保守的成员。在哺乳动物中,GnRH-II已被证明调节生殖和摄食行为。在雌性麝香鼩中,GnRH-II处理增加了交配行为,减少了食物摄入量。虽然已知含有GnRH-II的神经元位于中脑,但GnRH-II作用的神经部位尚不确定,GnRH-II受能量可用性调节的程度也不确定。为了确定GnRH-II的功能是否受到食物摄入变化的影响,我们分析了中脑中GnRH-II mRNA的水平和许多靶区GnRH-II蛋白的水平。成年麝香鼩被随意喂食,食物限制,或食物限制,并在不同的持续时间。与自由进食水平相比,进食限制减少,再进食90 min恢复,中脑GnRH-II mRNA水平和内侧缰和腹内侧核等多个靶区GnRH-II肽水平均有所下降。重新喂食90分钟也能恢复进食不足的鼩鼱的雌性性行为。在雄性鼩鼱中,大量的GnRH-II肽存在于所有被检测的部位,包括视前区,一个在雌性鼩鼱中只有低GnRH-II的区域。与雌性相比,食物限制不会影响雄性大脑中的GnRH-II蛋白或抑制它们的交配行为。我们的研究结果进一步明确了GnRH-II、能量平衡和生殖之间的关系,并表明食物限制可能通过减少GnRH-II向几个脑核的输出来抑制雌性生殖。我们假设这种高度保守的神经肽在包括人类在内的其他哺乳动物中也有类似的功能,可以在能量充足的时期微调生殖努力。
GnRH-II is the most evolutionarily conserved member of the GnRH peptide family. In mammals, GnRH-II has been shown to regulate reproductive and feeding behaviors. In female musk shrews, GnRH-II treatment increases mating behaviors and decreases food intake. Although GnRH-II-containing neurons are known to reside in the midbrain, the neural sites of GnRH-II action are undetermined, as is the degree to which GnRH-II is regulated by energy availability. To determine whether GnRH-II function is affected by changes in food intake, we analyzed the levels of GnRH-II mRNA in the midbrain and GnRH-II protein in numerous target regions. Adult musk shrews were ad libitum fed, food restricted, or food restricted and refed for varying durations. Compared with ad libitum levels, food restriction decreased, and 90 min of refeeding reinstated, GnRH-II mRNA levels in midbrain and GnRH-II peptide in several target areas including the medial habenula and ventromedial nucleus. Refeeding for 90 min also reinstated female sexual behavior in underfed shrews. In male shrews, abundant GnRH-II peptide was present in all sites assayed, including the preoptic area, a region with only low GnRH-II in females. In contrast to females, food restriction did not affect GnRH-II protein in male brains or inhibit their mating behavior. Our results further define the relationship between GnRH-II, energy balance, and reproduction, and suggest that food restriction may inhibit female reproduction by reducing GnRH-II output to several brain nuclei. We postulate that this highly conserved neuropeptide functions similarly in other mammals, including humans, to fine-tune reproductive efforts with periods of sufficient energy resources.