Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis

FEBS Lett. 2005 Aug 15;579(20):4465-9. doi: 10.1016/j.febslet.2005.07.014.

Abstract

Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+ fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the importance of LIF signaling for HPA axis development.

Publication types

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

MeSH terms

  • Adrenocorticotropic Hormone / analysis
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Hypothalamo-Hypophyseal System / embryology*
  • Hypothalamo-Hypophyseal System / metabolism
  • Interleukin-6 / metabolism
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Mice
  • Mice, Mutant Strains
  • Mifepristone / pharmacology
  • Mutation
  • Pituitary Gland, Anterior / immunology
  • Pituitary-Adrenal System / embryology*
  • Pituitary-Adrenal System / metabolism
  • Pro-Opiomelanocortin / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Corticotropin-Releasing Hormone / analysis
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology*
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Mineralocorticoid / metabolism
  • Receptors, OSM-LIF
  • Signal Transduction*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lif protein, mouse
  • Lifr protein, mouse
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, Cytokine
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Receptors, OSM-LIF
  • Tumor Necrosis Factor-alpha
  • Mifepristone
  • Pro-Opiomelanocortin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone