JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons

Eun Kyung Ko, Lynn P. Chorich, Megan E. Sullivan, Richard S Cameron, Lawrence C Layman

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume470
DOIs
StatePublished - Jul 15 2018

Fingerprint

Janus Kinases
Transcription
Transducers
Gene expression
Gonadotropin-Releasing Hormone
Neurons
Luteinizing Hormone
Nose
Gene Expression
Genes
STAT1 Transcription Factor
Pituitary Hormone-Releasing Hormones
Hypogonadism
Puberty
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Cell Movement
Reproduction
Proteins
Transcription Factors

Keywords

  • GnRH neurons
  • JAK/STAT pathway
  • NLT cells
  • Nasal embryonic LHRH factor (NELF)
  • cDNA array
  • shRNA lentiviral particles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons. / Ko, Eun Kyung; Chorich, Lynn P.; Sullivan, Megan E.; Cameron, Richard S; Layman, Lawrence C.

In: Molecular and Cellular Endocrinology, Vol. 470, 15.07.2018, p. 151-159.

Research output: Contribution to journalArticle

@article{72c7d6a2c2f6480b89d3ac8cd9adf4e1,
title = "JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons",
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.",
keywords = "GnRH neurons, JAK/STAT pathway, NLT cells, Nasal embryonic LHRH factor (NELF), cDNA array, shRNA lentiviral particles",
author = "Ko, {Eun Kyung} and Chorich, {Lynn P.} and Sullivan, {Megan E.} and Cameron, {Richard S} and Layman, {Lawrence C}",
year = "2018",
month = "7",
day = "15",
doi = "10.1016/j.mce.2017.10.009",
language = "English (US)",
volume = "470",
pages = "151--159",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in GnRH neurons

AU - Ko, Eun Kyung

AU - Chorich, Lynn P.

AU - Sullivan, Megan E.

AU - Cameron, Richard S

AU - Layman, Lawrence C

PY - 2018/7/15

Y1 - 2018/7/15

N2 - 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.

AB - 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.

KW - GnRH neurons

KW - JAK/STAT pathway

KW - NLT cells

KW - Nasal embryonic LHRH factor (NELF)

KW - cDNA array

KW - shRNA lentiviral particles

UR - http://www.scopus.com/inward/record.url?scp=85033572312&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033572312&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2017.10.009

DO - 10.1016/j.mce.2017.10.009

M3 - Article

C2 - 29050862

AN - SCOPUS:85033572312

VL - 470

SP - 151

EP - 159

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -