title: Loss of the pregnancy-induced rise in cortisol concentrations in the ewe impairs the fetal insulin-like growth factor axis.
abstract: Maternal cortisol levels increase during pregnancy. Although this change is important for optimal fetal growth, the mechanisms of the changes in growth remain unclear. The hypothesis examined was that alterations in maternal plasma cortisol concentrations are associated with changes in the fetal insulin-like growth factor (IGF) axis. Pregnant ewes in late gestation (115 ± 0.4 days) were studied: six control animals, five ewes given 1 mg kg(-1) day(-1) cortisol (high cortisol) and five adrenalectomised ewes given 0.5-0.6 mg kg(-1) day(-1) cortisol (low cortisol). Blood samples were taken throughout the experiment and at necropsy (130 ± 0.2 days) and fetal liver was frozen for mRNA analysis. Fetal IGF-I and insulin plasma concentrations were lower and insulin-like growth factor-binding protein-1 (IGFBP-1) concentrations were higher in the low cortisol group compared with those in the control group (P < 0.05). Fetal liver IGF-II and IGFBP-3 mRNA were decreased in low cortisol animals compared with controls (P < 0.05). There were no significant changes in these parameters in the high cortisol group, and there were no changes in fetal liver IGF-I, growth hormone receptor, IGF-I receptor, IGF-II receptor, IGFBP-1 or IGFBP-2 mRNA levels between the groups. These data suggest that reduced fetal IGF availability contributes to reduced fetal growth when maternal cortisol secretion is impaired, but not during exposure to moderate increases in cortisol.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Jensen
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
authors.forename: Mark
authors.initials: M
authors.lastname: Vickers
authors.forename: Bernhard
authors.initials: B
authors.lastname: Breier
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: Maureen
authors.initials: M
authors.lastname: Keller-Wood
mesh_terms: D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood*; D007262:Infusions, Intravenous; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D012756:Sheep; D015398:Signal Transduction; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D006854:Hydrocortisone