title: Hypothalamic and pituitary leukemia inhibitory factor gene expression in vivo: a novel endotoxin-inducible neuro-endocrine interface.
abstract: We have recently shown expression of leukemia inhibitory factor (LIF) in human fetal pituitary tissue and its in vitro induction of POMC transcription. We now use qualitative and semiquantitative RT-PCR to demonstrate that LIF and LIF-receptor (LIF-R) are constitutively expressed in the normal mouse hypothalamus and pituitary. Hypothalamic and pituitary LIF and LIF-R are significantly induced (up to 6- and 4-fold, respectively) in vivo in response to lipopolysaccharide endotoxin (LPS) administered to B6D2F1 and C57BL/6 mice. In contrast to the nearly exclusive expression of matrix-associated LIF messenger RNA (mRNA) in control hypothalamus and pituitary, both diffusible and matrix-associated LIF mRNA alternate transcripts are induced by LPS. Furthermore, the time course of peripheral ACTH-response to LPS peaks at 60 min, whereas hypothalamic LIF mRNA increase occurs at 30 min and pituitary LIF induction occurs at 60 min. These results show that mLIF is a novel LPS-inducible proinflammatory neuroendocrine cytokine and the alternatively spliced diffusible LIF may play a paracrine role in activating pituitary ACTH secretion in synergy with hypothalamic CRH, implying a mechanism for central nervous system cytokine responses to immune signals.
authors.affiliation: Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, Los Angeles, California 90048-1865, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: S G
authors.initials: SG
authors.lastname: Ren
authors.forename: S
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D017931:DNA Primers; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D015183:Restriction Mapping; D013045:Species Specificity; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017931:DNA Primers; D004731:Endotoxins; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008070:Lipopolysaccharides; D008222:Lymphokines; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin