title: Late gestation modulation of fetal glucocorticoid effects requires the receptor for leukemia inhibitory factor: an observational study.
abstract: BACKGROUND
  Ablation of the low-affinity receptor subunit for leukemia inhibitory factor (LIFR) causes multi-systemic defects in the late gestation fetus. Because corticosterone is known to have a broad range of effects and LIF function has been associated with the hypothalamo-pituitary-adrenal axis, this study was designed to determine the role for LIFR in the fetus when exposed to the elevated maternal glucocorticoid levels of late gestation. Uncovering a requirement for LIFR in appropriate glucocorticoid response will further understanding of control of glucocorticoid function.
  
  
  METHODS
  Maternal adrenalectomy or RU486 administration were used to determine the impact of the maternal glucocorticoid surge on fetal development in the absence of LIFR. The mice were analyzed by a variety of histological techniques including immunolabeling and staining techniques (hematoxylin and eosin, Alizarin red S and alcian blue). Plasma corticosterone was assayed using radioimmunoassay.
  
  
  RESULTS
  Maternal adrenalectomy does not improve the prognosis for LIFR null pups and exacerbates the effects of LIFR loss. RU486 noticeably improves many of the tissues affected by LIFR loss: bone density, skeletal muscle integrity and glial cell formation. LIFR null pups exposed during late gestation to RU486 in utero survive natural delivery, unlike LIFR null pups from untreated litters. But RU486 treated LIFR null pups succumb within the first day after birth, presumably due to neural deficit resulting in an inability to suckle.
  
  
  CONCLUSIONS
  LIFR plays an integral role in modulating the fetal response to elevated maternal glucocorticoids during late gestation. This role is likely to be mediated through the glucocorticoid receptor and has implications for adult homeostasis as a direct tie between immune, neural and hormone function.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA 98195-7190, USA. cware@u.washington.edu
authors.forename: Carol B
authors.initials: CB
authors.lastname: Ware
authors.forename: Angelique M
authors.initials: AM
authors.lastname: Nelson
authors.forename: Denny
authors.initials: D
authors.lastname: Liggitt
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000196:embryology / Q000235:genetics / Q000517:prevention & control; D003345:Corticosterone / Q000097:blood; D005260:Female; D005315:Fetal Diseases / Q000196:embryology / Q000235:genetics / Q000517:prevention & control; D005333:Fetus / Q000502:physiology*; D005804:Genes, Lethal; D005865:Gestational Age; D006706:Homeostasis; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000196:embryology / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects; D015213:Neuroimmunomodulation / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000502:physiology*; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology; D053606:Receptors, OSM-LIF; D013047:Specific Pathogen-Free Organisms; D013116:Spinal Cord / Q000196:embryology / Q000473:pathology
chemical_list: D006727:Hormone Antagonists; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D011506:Proteins; D018121:Receptors, Cytokine; D011965:Receptors, Glucocorticoid; D053606:Receptors, OSM-LIF; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone