促性腺激素释放激素(GnRH)神经元是大脑中的关键神经内分泌细胞,因为它们通过调节下丘脑-垂体-性腺轴功能来控制生殖。在这种情况下,抗苗勒管激素(AMH),生长激素(GH),和胰岛素样生长因子1(IGF1)在体外显示可改善GnRH神经元的迁移和功能。AMH,GH,IGF1信号通路参与体内GnRH神经元的发育和功能,然而,目前仍然未知。为了评估AMH的作用,GH,和IGF1系统在GnRH神经元发育中,我们评估了AMH受体(AMHR2)的表达,GH(GHR),和IGF1(IGF1R)在不同发育阶段的离体小鼠切片上。AMHR2、GHR、使用已建立的方案和商业抗体通过免疫荧光评估IGF1R。在E12.5、E14.5和E18.5分析小鼠的头部切片。特别是,在E12.5,我们关注的是犁鼻器官(VNO)的神经源性上皮,其中GnRH神经元,迁移团细胞,开创性的伏马鼻轴突出现了。在E14.5,我们专注于VNO和鼻前脑交界处(NFJ),GnRH神经元起源和迁移到下丘脑的两个区域,分别。在E18.5,中位数,这是释放GnRH的下丘脑区域,被分析。AtE12.5,doubletemperatingfortheneuronicmarkerβ-tubulinIIIandAMHR2,GHR,或IGF1R在早期胚胎发育过程中在嗅觉和VNO的神经源性壁龛中显示出信号。此外,IGF1R和GHR由出现VNO的GnRH神经元表达。在E14.5,发现神经元标记β-微管蛋白III相似的表达模式,而IGF1R和GHR的表达开始下降,正如在E18.5中观察到的那样。值得注意的是,标记为PLXND1的下丘脑GnRH神经元AMHR2表达检测为阳性。对小鼠切片的离体实验揭示了AMHR2,GHR,和IGF1R在神经源性区域和下丘脑区室之间的任何发育时间点。这些发现表明相关系统在GnRH神经元发育中的不同功能作用。
Gonadotropin-releasing hormone (GnRH) neurons are key neuroendocrine cells in the brain as they control reproduction by regulating hypothalamic-pituitary-gonadal axis function. In this context, anti-Müllerian hormone (AMH), growth hormone (GH), and insulin-like growth factor 1 (IGF1) were shown to improve GnRH neuron migration and function in vitro. Whether AMH, GH, and IGF1 signaling pathways participate in the development and function of GnRH neurons in vivo is, however, currently still unknown. To assess the role of AMH, GH, and IGF1 systems in the development of GnRH neuron, we evaluated the expression of AMH receptors (
AMHR2), GH (GHR), and IGF1 (IGF1R) on sections of ex vivo mice at different development stages. The expression of
AMHR2, GHR, and IGF1R was assessed by immunofluorescence using established protocols and commercial antibodies. The head sections of mice were analyzed at E12.5, E14.5, and E18.5. In particular, at E12.5, we focused on the neurogenic epithelium of the vomeronasal organ (VNO), where GnRH neurons, migratory mass cells, and the pioneering vomeronasal axon give rise. At E14.5, we focused on the VNO and nasal forebrain junction (NFJ), the two regions where GnRH neurons originate and migrate to the hypothalamus, respectively. At E18.5, the median eminence, which is the hypothalamic area where GnRH is released, was analyzed. At E12.5, double staining for the neuronal marker ß-tubulin III and
AMHR2, GHR, or IGF1R revealed a signal in the neurogenic niches of the olfactory and VNO during early embryo development. Furthermore, IGF1R and GHR were expressed by VNO-emerging GnRH neurons. At E14.5, a similar expression pattern was found for the neuronal marker ß-tubulin III, while the expression of IGF1R and GHR began to decline, as also observed at E18.5. Of note, hypothalamic GnRH neurons labeled for PLXND1 tested positive for
AMHR2 expression. Ex vivo experiments on mouse sections revealed differential protein expression patterns for
AMHR2, GHR, and IGF1R at any time point in development between neurogenic areas and hypothalamic compartments. These findings suggest a differential functional role of related systems in the development of GnRH neurons.