Sex hormones regulate CFTR in developing fetal rat lung epithelial cells.
Sex hormones modulate two normal processes of late-gestation mammalian lung development: the onset of augmented production of surfactant phospholipids and the loss of mesenchymal cells. As prenatal lung development advances, epithelial chloride secretory pathways diminish as opposing sodium absorptive pathways increase in expression. We hypothesized that sex hormones may influence both the gene expression and functional activity of the chloride channel known as the cystic fibrosis transmembrane conductance regulator (CFTR) in fetal lung epithelium. We report here that sex hormones exert opposite effects on CFTR. Androgen increases and estrogen decreases CFTR functional activity [as assessed by CFTR antisense (but not sense) oligodeoxynucleotide-sensitive adenosine 3',5'-cyclic monophosphate-stimulated cell volume reduction or by glibenclamide-sensitive, amiloride-insensitive transepithelial electrical potential] in primary cultures of fetal rat lung epithelial cells. No alterations in CFTR mRNA levels measured by quantitative polymerase chain reaction amplification of reverse transcripts) accompanied either the changes in functional activity induced by sex hormones or the changes observed during normal development, suggesting that sex hormone modulation of CFTR in antenatal lung occurs at a posttranscriptional level. Our data are consistent with the hypothesis that both androgen and estrogen contribute to the male disadvantage with respect to fetal lung functional development.
Sweezey
N B
NB
McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
Ghibu
F
F
Gagnon
S
S
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells; D004848:Epithelium / Q000196:embryology; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005865:Gestational Age; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000196:embryology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D013755:Tetradecanoylphorbol Acetate