Nov 1, 2008

GNRH induces the unfolded protein response in the LbetaT2 pituitary gonadotrope cell line

Molecular Endocrinology
Minh-Ha T DoMark A Lawson


The neuropeptide GNRH 1 stimulates the secretion of the reproductive hormone LH in pituitary gonadotropes. Other secretory cell types depend on the unfolded protein response (UPR) pathway to regulate protein synthesis and protect against endoplasmic reticulum (ER) stress in response to differentiation or secretory stimuli. This study investigated the role of the UPR in GNRH action within the LbetaT2 gonadotrope model. Cells were treated with GNRH, and the activation of UPR signaling components and general translational status was examined. The ER-resident stress sensors, Atf6, Eif2ak3, and Ern1, are all present, and GNRH stimulation results in the phosphorylation of eukaryotic translation initiation factor 2A kinase 3 and its downstream effector, eukaryotic translation initiation factor 2A. Additionally, activation of the UPR was confirmed both in LbetaT2 as well as mouse primary pituitary cells through identifying GNRH-induced splicing of Xbp1 mRNA, a transcription factor activated by splicing by the ER stress sensor, ER to nucleus signaling 1. Ribosome profiling revealed that GNRH stimulation caused a transient attenuation in translation, a hallmark of the UPR, remodeling ribosomes from actively translating polysomes to trans...Continue Reading

Mentioned in this Paper

Biochemical Pathway
X-Box Binding Protein 1
ATF6 gene
Set of Polysomal Ribosomes
Ribonucleoprotein Activity
Unfolded Protein Response
Complex (molecular entity)
Pituitary Diseases

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