Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone

Mol Endocrinol. 2000 Nov;14(11):1811-9. doi: 10.1210/mend.14.11.0550.

Abstract

The neuropeptide GnRH is a central regulator of mammalian reproductive function produced by a dispersed population of hypothalamic neurosecretory neurons. The principal action of GnRH is to regulate release of the gonadotropins, LH and FSH, by the gonadotrope cells of the anterior pituitary. Using a cultured cell model of mouse pituitary gonadotrope cells, alphaT3-1 cells, we present evidence that GnRH stimulation of alphaT3-1 cells results in an increase in cap-dependent mRNA translation. GnRH receptor activation results in increased protein synthesis through a regulator of mRNA translation initiation, eukaryotic translation initiation factor 4E-binding protein, known as 4EBP or PHAS (protein, heat, and acid stable). Although the GnRH receptor is a member of the rhodopsin-like family of G protein-linked receptors, we show that activation of translation proceeds through a signaling pathway previously described for receptor tyrosine kinases. Stimulation of translation by GnRH is protein kinase C and Ras dependent and sensitive to rapamycin. Furthermore, GnRH may also regulate the cell cycle in alphaT3-1 cells. The activation of a signaling pathway that regulates both protein synthesis and cell cycle suggests that GnRH may have a significant role in the maintenance of the pituitary gonadotrope population in addition to directing the release of gonadotropins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins*
  • Cell Cycle Proteins
  • Cells, Cultured
  • Encephalomyocarditis virus / genetics
  • Eukaryotic Initiation Factors
  • Genes, ras
  • Gonadotropin-Releasing Hormone / metabolism*
  • Gonadotropin-Releasing Hormone / pharmacology
  • Insulin / pharmacology
  • Mice
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Pituitary Gland / cytology*
  • Pituitary Gland / drug effects
  • Pituitary Gland / physiology*
  • Protein Biosynthesis*
  • Protein Kinase C / metabolism
  • Protein Kinases*
  • Protein Subunits
  • RNA Caps / genetics
  • RNA, Messenger / genetics
  • Receptors, LHRH / biosynthesis
  • Receptors, LHRH / genetics
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases

Substances

  • 5' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Insulin
  • Phosphoproteins
  • Protein Subunits
  • RNA Caps
  • RNA, Messenger
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • Protein Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Protein Kinase C
  • Sirolimus