Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2. Lin TY et al. Neuromedin U (NMU) was originally identified as an anorexigenic peptide that modulates appetite as well as energy homeostasis through the brain-gut axis. Although growing evidence has linked NMU activity with the development of female reproductive organs, no direct expression of and function for NMU in these organs has been pinpointed. Using a superovulated rat model, we found that NMU is directly expressed in the ovary, where its transcript level is tightly regulated by gonadotropins. Ovarian microdissection and immunohistochemical staining showed clearly that NMU is expressed mainly in theca/interstitial cells and to a moderate extent in granulosa cells. Primary cell studies together with reporter assays indicated the Nmu mRNA level in these cells is strongly induced via cAMP signaling, whereas this increase in expression can be reversed by the degradation message residing within its 3'-untranslated region, which recruits cis-acting mRNA degradation mechanisms, such as the gonadotropin-induced zinc finger RNA-binding protein Zfp36l1. This study also demonstrated that NMUR2, but not NMUR1, is the dominant NMU receptor in the ovary, where its expression is restricted to theca/interstitial cells. Treatment with NMU led to induction of the early-response c-Fos gene, phosphorylation of ERK1/2 and promotion of progesterone production in both developing and mature theca/interstitial cells. Taken as a whole, this study demonstrates that NMU and NMUR2 compose a novel autocrine system in theca/interstitial cells in which the intensity of signaling is tightly controlled by gonadotropins.
Expression regulated by
FSH, LH
Comment
Ovarian localization
Granulosa, Theca
Comment
This gene was found in an ovualtion DNA array.
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Regulation of gonadotropin secretion and puberty onset by neuromedin U. Fukue Y et al. Neuromedin U (NMU), an anorexigenic peptide, was originally isolated from porcine spinal cord in 1985. As NMU is abundant in the anterior pituitary gland, we investigated the effects of NMU on gonadotropin secretion. Both NMU and its receptors, NMUR1 and NMUR2, were expressed in the pituitary gland. NMU suppressed LH and FSH releases from rat anterior pituitary cells. Moreover, NMU-deficient mice exhibit an early onset of vaginal opening. The LHbeta/FSHbeta ratio, which is an index of puberty onset, is high in young NMU-deficient mice. These results indicate that NMU suppresses gonadotropin secretion and regulates the onset of puberty.