Abstract
The neuropeptide gonadotropin-releasing hormone stimulates synthesis and secretion of the glycoprotein gonadotropic hormones and activates the unfolded protein response, which causes a transient reduction of endoplasmic reticulum-associated mRNA translation. Hormone-treated cell extracts were fractionated to resolve mRNA in active polyribosomes from mRNA in inactive complexes. Quantitative real-time PCR and expression array analysis were used to determine hormone-induced redistribution of mRNAs between fractions and individual mRNAs were found to be redistributed differentially. Among the affected mRNAs relevant to gonadotropin synthesis, the luteinizing hormone subunit genes Lhb and Cga were enriched in the ribonucleoprotein pool. The MAP kinase phosphatase Dusp1 was enriched in the polyribosome pool. Enrichment of Dusp1 mRNA in the polyribosome pool was independent of the unfolded protein response, sensitive to ERK inhibition, and dependent on the 3'untranslated region. The results show that GnRH exerts translational control to modulate physiologically relevant gene expression through two distinct signaling pathways.