Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
Mol Cells. 2011 Aug;32(2):203-7. doi: 10.1007/s10059-011-0086-7. Epub 2011 Jun 1.
NELL2, a protein containing epidermal growth factor-like repeat domains, is predominantly expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. Previously we found that NELL2 is involved in the onset of female puberty by regulating the release of gonadotropin-releasing hormone (GnRH), and in normal male sexual behavior by controlling the development of the sexually dimorphic nucleus of the preoptic area (POA). In this study we investigated the effect of NELL2 on the female rat estrous cycle. NELL2 expression in the POA was highest during the proestrous phase. NELL2 mRNA levels in the POA were increased by estrogen treatment in ovariectomized female rats. Blocking NELL2 synthesis in the female rat hypothalamus decreased the expression of kisspeptin 1, an important regulator of the GnRH neuronal apparatus, and resulted in disruption of the estrous cycle at the diestrous phase. These results indicate that NELL2 is involved in the maintenance of the normal female reproductive cycle in mammals.
NELL2 是一种富含表皮生长因子样重复结构域的蛋白，主要在神经系统中表达。在哺乳动物大脑中，NELL2 的表达主要是神经元。我们之前发现，NELL2 通过调节促性腺激素释放激素（GnRH）的释放来参与女性青春期的开始，并通过控制视前区（POA）的性别二态性核的发育来控制正常的雄性性行为。在这项研究中，我们研究了 NELL2 对雌性大鼠发情周期的影响。POA 中的 NELL2 表达在发情前期最高。雌激素处理去卵巢雌性大鼠的 POA 中 NELL2 mRNA 水平增加。阻断雌性大鼠下丘脑的 NELL2 合成会降低 kisspeptin1 的表达，而 kisspeptin1 是 GnRH 神经元装置的重要调节剂，会导致发情周期在动情期中断。这些结果表明，NELL2 参与维持哺乳动物正常的生殖周期。
