Zhou S S, Li P
Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
Genet Mol Res. 2014 Aug 28;13(3):6672-82. doi: 10.4238/2014.August.28.12.
Neural tissue-specific epidermal growth factor-like repeat domain-containing protein (NELL2) was previously found to play an important role in nerve growth, neural differentiation, neural elasticity, synaptic transport, and vesicle release. In this study, we examined the effect of NELL2 on gonadotropin-releasing hormone (GnRH) neurons and the initiation of puberty in female rats. We studied changes in NELL2 mRNA and protein expression at different stages of sexual development (postnatal days 30, 35, and 45) in female rats to determine the impact of NELL2 on GnRH mRNA expression. We also investigated the influence on the vulva-opening age by inhibiting NELL2 mRNA expression through lentiviral vector-mediated RNA interference. The intraventricular administration of an NELL2-interfering virus reduced NELL2 and GnRH expression at multiple stages of sexual development and delayed the age of vulva-opening in female rats. These results demonstrate that lentiviral-mediated RNA interference technology can be used for targeted regulation of sexual development in vivo. In addition, we found that NELL2 regulated the initiation of puberty in female rats.
神经组织特异性含表皮生长因子样重复结构域蛋白(NELL2)先前被发现于神经生长、神经分化、神经弹性、突触运输和囊泡释放中发挥重要作用。在本研究中,我们检测了NELL2对促性腺激素释放激素(GnRH)神经元及雌性大鼠青春期启动的影响。我们研究了雌性大鼠性发育不同阶段(出生后第30、35和45天)NELL2 mRNA和蛋白表达的变化,以确定NELL2对GnRH mRNA表达的影响。我们还通过慢病毒载体介导的RNA干扰抑制NELL2 mRNA表达,研究其对外阴开口年龄的影响。脑室内注射NELL2干扰病毒降低了性发育多个阶段的NELL2和GnRH表达,并延迟了雌性大鼠的外阴开口年龄。这些结果表明,慢病毒介导的RNA干扰技术可用于体内性发育的靶向调控。此外,我们发现NELL2调节雌性大鼠青春期的启动。