title: Is the fetal lung a mineralocorticoid receptor target organ? Induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine.
abstract: BACKGROUND
  Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life.
  
  
  OBJECTIVE
  This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), and of MR- and GR-regulated genes and proteins, serum and glucocorticoid-induced kinase (Sgk-1), epithelial sodium channel (ENaC alpha), and Na,K-ATPase alpha1.
  
  
  METHODS
  Lung, renal cortex and medulla, and small intestine were collected from fetuses at 80, 100, 120, 130 and 145 days' gestation and from day 1 and 7 neonatal lambs. Real-time PCR was performed to determine mRNA concentration for MR, GR, the 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD1 and 2), Sgk-1, ENaC alpha, and Na,K-ATPase alpha1. Protein expression of ENaC alpha and Na,K-ATPase alpha1 in whole cell and membrane fractions was determined by immunoblotting.
  
  
  RESULTS
  Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally. In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11 beta-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaC alpha increased by 120 days, peaking at 145 days, and Na,K-ATPase alpha1 was greatest at 130 days.
  
  
  CONCLUSIONS
  The expression of high levels of MR and 11 beta-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption.
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA. kellerwd@cop.ufl.edu
authors.forename: Maureen
authors.initials: M
authors.lastname: Keller-Wood
authors.forename: Marcela
authors.initials: M
authors.lastname: von Reitzenstein
authors.forename: Jarret
authors.initials: J
authors.lastname: McCartney
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000196:embryology / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005333:Fetus / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007421:Intestine, Small / Q000196:embryology / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D012756:Sheep; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000305:Adrenal Cortex Hormones; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D017346:Protein Serine-Threonine Kinases; D000254:Sodium-Potassium-Exchanging ATPase
references.citation: J Neurosci. 1998 Apr 1;18(7):2570-80
references.pmid: 9502816
references.citation: Endocrinology. 1992 Nov;131(5):2120-6
references.pmid: 1425412
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L217-30
references.pmid: 11404265
references.citation: Am J Physiol. 1998 Jun;274(6):F1062-9
references.pmid: 9841497
references.citation: Neonatology. 2008;93(4):257-62
references.pmid: 18032912
references.citation: Pediatrics. 1972 Oct;50(4):515-25
references.pmid: 4561295
references.citation: J Clin Endocrinol Metab. 1998 Dec;83(12):4490-7
references.pmid: 9851798
references.citation: J Appl Physiol (1985). 2002 Oct;93(4):1542-8
references.pmid: 12235057
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L631-41
references.pmid: 11880287
references.citation: J Endocrinol. 1982 Oct;95(1):71-9
references.pmid: 7130892
references.citation: J Endocrinol. 1993 May;137(2):213-22
references.pmid: 8326249
references.citation: J Soc Gynecol Investig. 2005 Feb;12(2):84-91
references.pmid: 15695102
references.citation: Physiol Rev. 2002 Jul;82(3):735-67
references.pmid: 12087134
references.citation: Exp Physiol. 1995 May;80(3):457-67
references.pmid: 7640010
references.citation: Mol Endocrinol. 2001 Apr;15(4):575-88
references.pmid: 11266509
references.citation: Biochem Biophys Res Commun. 1999 Dec 9;266(1):5-14
references.pmid: 10581156
references.citation: Cell Physiol Biochem. 2003;13(1):21-8
references.pmid: 12649599
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L73-80
references.pmid: 12948937
references.citation: Mol Cell Endocrinol. 1999 Nov 25;157(1-2):153-60
references.pmid: 10619406
references.citation: Eur J Pharmacol. 1993 Oct 15;247(2):145-54
references.pmid: 8282004
references.citation: Horm Metab Res. 2002 Oct;34(10):537-44
references.pmid: 12439780
references.citation: Am J Physiol. 1996 Jan;270(1 Pt 2):R33-40
references.pmid: 8769782
references.citation: Nature. 1985 Aug 22-28;316(6030):691-5
references.pmid: 2993903
references.citation: J Soc Gynecol Investig. 2003 Dec;10(8):480-9
references.pmid: 14662161
references.citation: Recent Prog Horm Res. 1973;29:111-59
references.pmid: 4356273
references.citation: Kidney Int. 2002 Feb;61(2):405-13
references.pmid: 11849380
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 1):L227-33
references.pmid: 9252560
references.citation: Nat Genet. 1996 Mar;12(3):325-8
references.pmid: 8589728
references.citation: Am J Physiol Cell Physiol. 2002 Sep;283(3):C762-72
references.pmid: 12176733
references.citation: Comp Biochem Physiol B. 1989;94(1):1-11
references.pmid: 2513162
references.citation: Annu Rev Physiol. 2004;66:77-101
references.pmid: 14977397
references.citation: Neonatology. 2007;91(4):217-21
references.pmid: 17568152
references.citation: Semin Nephrol. 1990 Jul;10(4):311-9
references.pmid: 2200094
references.citation: Reproduction. 2004 Jun;127(6):717-25
references.pmid: 15175508
references.citation: Am J Physiol. 1995 Oct;269(4 Pt 2):R881-7
references.pmid: 7485607
references.citation: J Pediatr Gastroenterol Nutr. 1985 Dec;4(6):893-901
references.pmid: 4067777
references.citation: Am J Physiol. 1995 Sep;269(3 Pt 1):C805-12
references.pmid: 7573414
references.citation: Pediatr Res. 1984 Jul;18(7):607-11
references.pmid: 6089082
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Ciba Found Symp. 1977;(47):5-30
references.pmid: 205398
references.citation: Biol Neonate. 2006;89(2):109-19
references.pmid: 16195667
references.citation: J Steroid Biochem. 1981 Sep;14(9):811-7
references.pmid: 6946266
references.citation: Steroids. 1996 Apr;61(4):263-9
references.pmid: 8733012
references.citation: Hypertension. 2002 Nov;40(5):729-34
references.pmid: 12411469
references.citation: Am J Respir Cell Mol Biol. 1996 Jun;14(6):599-607
references.pmid: 8652188
references.citation: Pediatr Res. 1985 Oct;19(10):1048-52
references.pmid: 3903645
references.citation: Am J Physiol. 1999 Jul;277(1):L197-203
references.pmid: 10409248
references.citation: Dev Pharmacol Ther. 1980;1(4):201-16
references.pmid: 7002509
references.citation: Pediatr Pulmonol. 2001 Jul;32(1):76-91
references.pmid: 11416880
references.citation: J Physiol. 1995 Nov 15;489 ( Pt 1):235-41
references.pmid: 8583407
references.citation: Physiol Res. 2004;53 Suppl 1:S63-80
references.pmid: 15119937
references.citation: Reprod Fertil Dev. 1995;7(5):1329-32
references.pmid: 8848607
references.citation: Acta Endocrinol (Copenh). 1993 Aug;129(2):169-77
references.pmid: 8372603
references.citation: Neuroendocrinology. 2003 Jan;77(1):2-14
references.pmid: 12624536