Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone.
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.
Sosnowski
R
R
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674, USA.
Mellon
P L
PL
Lawson
M A
MA
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004686:Encephalomyocarditis virus / Q000235:genetics; D039642:Eukaryotic Initiation Factors; D011905:Genes, ras; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases; D021122:Protein Subunits; D012315:RNA Caps / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011966:Receptors, LHRH / Q000096:biosynthesis / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D007328:Insulin; D010750:Phosphoproteins; D021122:Protein Subunits; D012315:RNA Caps; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C; D020123:Sirolimus