title: Leukemia-inhibitory factor-neuroimmune modulator of endocrine function.
abstract: Leukemia-inhibitory factor (LIF) is a pleiotropic cytokine expressed by multiple tissue types. The LIF receptor shares a common gp130 receptor subunit with the IL-6 cytokine superfamily. LIF signaling is mediated mainly by JAK-STAT (janus-kinase-signal transducer and activator of transcription) pathways and is abrogated by the SOCS (suppressor-of cytokine signaling) and PIAS (protein inhibitors of activated STAT) proteins. In addition to classic hematopoietic and neuronal actions, LIF plays a critical role in several endocrine functions including the utero-placental unit, the hypothalamo-pituitary-adrenal axis, bone cell metabolism, energy homeostasis, and hormonally responsive tumors. This paper reviews recent advances in our understanding of molecular mechanisms regulating LIF expression and action and also provides a systemic overview of LIF-mediated endocrine regulation. Local and systemic LIF serve to integrate multiple developmental and functional cell signals, culminating in maintaining appropriate hormonal and metabolic homeostasis. LIF thus functions as a critical molecular interface between the neuroimmune and endocrine systems.
authors.affiliation: Academic Affairs, Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, 90048, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Auernhammer
authors.forename: S
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000818:Animals; D004702:Endocrine Glands / Q000502:physiology*; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis; D006801:Humans; D007109:Immunity; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015394:Molecular Structure; D009424:Nervous System Physiological Phenomena; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology; D053606:Receptors, OSM-LIF; D015398:Signal Transduction
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF