The role of hypothalamic neuropeptides in the regulation of gonadotropins

点击翻译按钮获取中文摘要

In this present study, we examined the expression of MKP-1 by GnRH stimulation and investigated the possible role of MKP-1 on gonadotropin gene expression using gonadotroph cell line, LβT2 cells. MKP-1 expression was remarkably increased 60minutes after GnRH stimulation and ERK activation was gradually decreased after 60minutes. GnRH-induced ERK activation was completely inhibited in the presence of U0126, a MEK inhibitor, whereas GnRH-induced MKP-1 expression was partially inhibited by U0126. GnRH-induced MKP-1 induction was inhibited by dose dependently in the presence of triptolide, a diterpenoid triepoxide. On the other hand, ERK activation was potentiated at this time by this compound. U0126 prevented GnRH-stimulated gonadotropin LHβ and FSHβ subunit promoter activity by dose dependently. Whereas, GnRH-stimulated LHb and FSHb promoter activities were almost completely inhibited by triptolide. In addition, under pulsatile GnRH stimulation, MKP-1 expression was observed in high frequency GnRH pulse which preferentially increase LHb, but not in low frequency pulse under which FSHb preferentially increased. Our study demonstrated that MKP-1 induced by GnRH works not only as an ERK-inactivating phosphatase, but also as an important mediator which control gonadotoropin subunit gene expressions.