title: Regulation of insulin-like growth factor-II gene expression in the ovine fetal adrenal gland by adrenocorticotropic hormone and cortisol.
abstract: Maturation and activation of the fetal adrenal gland is crucial to fetal organ maturation and the onset of parturition in sheep. Insulin-like growth factors (IGFs) have been demonstrated to promote fetal adrenal mitogenesis and steroidogenesis in some species. Our previous studies showed that IGF-II mRNA is expressed in the steroidogenic cells of the fetal sheep adrenal, suggesting that IGF-II may be an important regulator of fetal adrenal function. However, the regulation of IGF-II gene expression is poorly understood. In the present study we measured the changes in IGF-II mRNA level in fetal sheep adrenals during late gestation in response to ACTH and cortisol. Either saline (0.5 ml/h) or cortisol (1 mg/24 h) was infused for 100 h to fetal sheep beginning on day 95 or 96 of pregnancy, or saline (0.5 ml/h), ACTH (0.5 micrograms/h) or cortisol (1 mg/h) was infused for 84 h to fetal sheep beginning on days 120-125 of pregnancy (term = 145 days). Adrenal RNA was subjected to Northern blot analysis with an ovine IGF-II cDNA probe. The relative abundance of total IGF-II mRNA decreased significantly in the ACTH- and cortisol-treated fetuses. IGF-II mRNA was localized by in situ hybridization using a 35S-labeled antisense ovine IGF-II cRNA probe, and IGF-II peptide was localized by immunohistochemistry. There were no differences in the cellular distribution patterns of IGF-II mRNA and IGF-II peptide after treatments, but the intensity of the hybridization signal for IGF-II mRNA and of immunostaining for IGF-II peptide decreased in adrenals from fetuses treated with ACTH or cortisol. These results suggest that ACTH and cortisol decrease IGF-II gene expression in the ovine fetal adrenal. We speculate that the cortisol surge observed in the late gestation ovine fetus may be responsible for down-regulation of IGF-II gene expression in the fetal adrenal at or just before birth.
authors.affiliation: Lawson Research Institute, St. Joseph's Health Center, London, Ontario, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Lü
authors.forename: V K
authors.initials: VK
authors.lastname: Han
authors.forename: W K
authors.initials: WK
authors.lastname: Milne
authors.forename: M
authors.initials: M
authors.lastname: Fraser
authors.forename: A M
authors.initials: AM
authors.lastname: Carter
authors.forename: E T
authors.initials: ET
authors.lastname: Berdusco
authors.forename: J R
authors.initials: JR
authors.lastname: Challis
mesh_terms: D000311:Adrenal Glands / Q000196:embryology* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000187:drug effects*; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology*; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone