Leukemia-Inhibitory Factor—Neuroimmune Modulator of Endocrine Function1
C. J. Auernhammer2 and
S. Melmed
Academic Affairs, Cedars-Sinai Research Institute, University of
California Los Angeles School of Medicine, Los Angeles, California
90048
Leukemia-inhibitory factor (LIF) is a pleiotropic cytokine expressedby
multiple tissue types. The LIF receptor shares a common gp130receptor
subunit with the IL-6 cytokine superfamily. LIF signalingis mediated
mainly by JAK-STAT (janus-kinase-signal transducerand activator of
transcription) pathways and is abrogated bythe SOCS
(suppressor-of cytokine signaling) and PIAS (proteininhibitors of
activated STAT) proteins. In addition to classichematopoietic and
neuronal actions, LIF plays a critical rolein several endocrine
functions including the utero-placentalunit, the
hypothalamo-pituitary-adrenal axis, bone cell metabolism,energy
homeostasis, and hormonally responsive tumors. This paperreviews
recent advances in our understanding of molecular mechanismsregulating
LIF expression and action and also provides a systemicoverview of
LIF-mediated endocrine regulation. Local and systemicLIF serve to
integrate multiple developmental and functionalcell signals,
culminating in maintaining appropriate hormonaland metabolic
homeostasis. LIF thus functions as a criticalmolecular interface
between the neuroimmune and endocrine systems.
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