JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons. (15th July 2018)

• Record Type: Journal Article
• Authors: Ko, Eun Kyung; Chorich, Lynn P.; Sullivan, Megan E.; Cameron, Richard S.; Layman, Lawrence C.
• Is Part Of: Molecular and cellular endocrinology. Volume 470(2018)
• Page Start: 151
• Page End: 159
• Publication Date: 2018-07-15
• Subjects: Nasal embryonic LHRH factor (NELF) -- GnRH neurons -- NLT cells -- cDNA array -- shRNA lentiviral particles -- JAK/STAT pathway; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.10.009
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Hypothalamic gonadotropin releasing hormone (GnRH) is crucial for the proper function of the hypothalamic-pituitary-gonadal (HPG) axis, subsequent puberty, and reproduction. When GnRH neuron migration or GnRH regulation is impaired, hypogonadotropic hypogonadism results. Mutations in the gene for nasal embryonic luteinizing hormone-releasing factor ( NELF ) have been identified in GnRH-deficient humans. NELF is a predominantly nuclear protein that may participate in gene transcription, but the genes NELF regulates are unknown. To address this question, RNA was extracted from NLT GnRH neuronal cells following either stable Nelf knockdown or scrambled control and subjected to cDNA arrays. Transcription factors and cell migration gene expression was altered most commonly. Members of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, including Stat1, Stat2, Stat5a, Jak2, Irf7 and Irf9, were significantly down regulated as assessed by RT-qPCR. Protein levels of STAT1, phospho-STAT1, and JAK2 were reduced, but the protein level of phospho-JAK2 was not. These findings suggest a role for NELF in the regulation of the JAK/STAT signaling pathway, which have important functions in GnRH neurons. Highlights: Nelf knockdown in NLT GnRH neurons was associated with reduced JAK/STAT expression. With Nelf knockdown, genes involved in transcription and migration were most affected. NELF co-localizes with RNA polymerase II. Evidence suggests that NELF affects transcription of the JAK/STAT pathway.