Oxytocin modulates mTORC1 pathway in the gut

Biochem Biophys Res Commun. 2013 Mar 15;432(3):466-71. doi: 10.1016/j.bbrc.2013.01.121. Epub 2013 Feb 11.

Abstract

Our recent findings of a weaning-related pattern of oxytocin (OT) and OT receptor (OTR) expression in the rat enteric nervous system and in villus-crypt enterocytes, together with the known high level and stability of OT in breast milk support that OT may play a role in gut function and development. We previously described a biphasic dose-response of the PI3K/Akt pathway in gut cells treated with OT. Activation peaked at 62.5 nM OT (30 min) and coincided with OTR internalization. Here we use automated Western blotting to further explore OT-elicited changes in Akt and pAkt(T308), as well as in downstream substrates p70 S6 kinase-1 (S6K1) and eIF-4E binding protein 1 (4E-BP1). Relative to fresh growth medium (FGM) alone, our results showed OT in FGM reduced the abundance and phosphorylation of S6K1 and the phosphorylation of 4E-BP1, both substrates of mammalian target of rapamycin complex 1 (mTORC1). Phosphorylation of mTORC1 regulator, Raptor(S792), was increased by high and low OT concentrations, with predicted inhibitory effects on mTORC1. OT thus downregulates anabolic effects induced by FGM activity catalyzed by mTORC1. OT is a regulator of the PI3K/Akt/mTORC1 pathway in Caco2BB cells and may modulate translation in gut cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Caco-2 Cells
  • Eukaryotic Initiation Factor-4E / metabolism
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / enzymology*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Oxytocin / pharmacology
  • Oxytocin / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Regulatory-Associated Protein of mTOR
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Eukaryotic Initiation Factor-4E
  • Multiprotein Complexes
  • RPTOR protein, human
  • Regulatory-Associated Protein of mTOR
  • Oxytocin
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1