Characterization of the roles of Neuromedin U signaling in the female reproductive system

• Main Authors: Ting-Yu Lin, 林庭宇
• Other Authors: Ching-Wei Luo
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/48562093363600831402

博士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 104 === Neuromedin U (NMU) is a neuropeptide that regulates multi-physiological functions through activation of NMUR1 or NMUR2. However, its function has not been elucidated in the female reproductive system. In the ovary, NMU expression was detected moderately in granulosa cells and co-expressed mainly with NMUR2 in theca cells. The fluctuation of NMU was regulated by gonadotropin-driven cAMP signaling and cAMP-mediated RNA-binding protein Zfp36l1, a cis-acting mRNA degradation mechanism. Furthermore, NMU treatment promoted the production of progesterone but not androstenedione in the developing and mature theca/interstitial cells. Thus, these results suggest that gonadotropin-stimulated NMU production controls the progesterone-related physiological roles through NMUR2 in the ovary. In the uterus, NMU and NMUR2 were not only expressed in the endometrial epithelial cells in mouse but also upregulated in the high-graded endometrial cancers in human. In the cell lines isolated from patients with high-graded endometrial cancer, NMU signaling could promote the expression and/or the nuclear translocation of mesenchymal markers. It also could sustain the level of adhesion signaling and this further regulated the cell motility and anchorage-independent growth. Further, NMU signaling also enhanced the EGF- and TGFβ1-mediated expression of mesenchymal markers. It also helped the maintenance of cell division of endometrial cancer cells in vivo. Together, these results suggest that the upregulated NMU signaling may be involved in the metastasis and tumor growth of high-graded endometrial cancer.