Function of hCG/LH and their receptor in the mammalian nervous system

携带激活突变的黄体生成素/促性腺激素受体基因突变的个体会发生家族性男性受限的性早熟，并经常有行为问题。FMPP患者出现的行为问题可能与受体突变导致的脑细胞功能障碍有关。最近的研究表明，人绒毛膜促性腺激素(HCG)及其受体(LH/CG-R)可能具有重要的生理功能。在神经系统中，黄体生成素/卵泡刺激素受体在哺乳动物的大脑中以时间和空间模式表达。体内应用hCG可促进神经再生，体外可促进原代神经元突起生长和存活。然而，人绒毛膜促性腺激素及其受体在神经系统中的功能仍不清楚。 为了了解hCG及其受体在哺乳动物神经系统发育中的作用，我们研究了转基因对大鼠肾上腺嗜铬细胞瘤双能细胞系PC12分化的影响。我们的研究表明，hCG的分化作用具有配体剂量和时间依赖性。细胞外信号调节蛋白激酶(ERKs)和p38丝裂原活化蛋白激酶(MAPK)在细胞分化过程中都是不可或缺的。此外，磷脂酶C(PLC)途径部分参与了hCG诱导PC12的分化。这些发现暗示了hCG/Lh和Lh/Cg-R在哺乳动物神经系统神经发生中的潜在作用。我们的研究还表明，hCG通过诱导髓鞘蛋白零(P0)的表达来促进髓鞘形成。这些研究结果表明，hCG/LH及其受体参与哺乳动物神经系统的发育和维持。人绒毛膜促性腺激素可能是未来治疗急性神经损伤或神经退行性疾病的一种潜在的再生药物。

Individuals with LH/CG-R carrying activating mutations develop familial male-limited precocious puberty and often have behavioral problems. The behavioral problem seen in patients with FMPP patients may be related to dysfunction of brain cells caused by the mutated receptor. Recent studies demonstrated human chorionic gonadotropin (hCG) and its receptor (LH/CG-R) may have nongonadal functions which could be important physiologically. In the nervous system LH/CG-R is expressed in the mammalian brain in a temporal and spatial pattern. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. However, the function of hCG and its receptor in the nervous system remains unclear. To understand the role of hCG and its receptor in the development of the mammalian nervous system, we studied the effect of the transgenes on the differentiation of the bipotent cell line, PC12, derived from rat adrenal pheochromocytoma. Our studies showed that the differentiation effect of hCG was ligand dose- and time-dependent. Both the extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (MAPK) were indispensable for the differentiation process. In addition, the Phospholipase C (PLC) pathway was partially involved in hCG induced PC12 differentiation. These findings imply a potential role of hCG/LH and LH/CG-R in the neurogenesis of the mammalian nervous system. Our studies also suggested that hCG promotes myelination through inducing myelin protein zero (P0) expression. the findings of these studies suggest that hCG/LH and its receptor participate in the development and maintenance of the mammalian nervous system. hCG may be a potential regeneration drug for future treatment of acute neural injuries or neurodegenerative disorders.