Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung.
Our purpose was to elucidate why clinical studies have up to now failed to demonstrate a positive effect of TRH combined with glucocorticosteroids on fetal lung maturity. Morphological and biochemical lung maturation were determined by electron microscopy, choline incorporation, and surfactant-protein-A m-RNA synthesis in rat lung organoid cultures after exposure with a series of concentrations of dexamethasone, triiodothyronine, and dimethyl-isopropyl-thyronine. Thyroid hormones improved morphogenesis of lung histotypic structures but had a negative effect on surfactant synthesis whereas glucocorticosteroids had a positive effect on the surfactant synthesis but a negative effect on morphogenesis. The combination of both substances even had the most negative effect on morphogenesis. Since morphogenesis of lung histotypic structures is prerequisite for surfactant synthesis and secretion, we hypothesize that a sequential treatment of thyroid hormones to improve morphogenesis followed by the application of glucocorticosteroids might be an option to improve neonatal lung function.
Hundertmark
S
S
Department of Obstetrics and Gynecology, Benjamin Franklin University Hospital, Free University Berlin, Germany. hundertmark@ukbf.fu-berlin.de
Ragosch
V
V
Zimmermann
B
B
Halis
G
G
Arabin
B
B
Weitzel
H K
HK
D000818:Animals; D015152:Blotting, Northern; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000032:analysis / Q000096:biosynthesis; D011247:Pregnancy; D011510:Proteolipids / Q000032:analysis / Q000096:biosynthesis; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control*; D013970:Thyronines / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D005938:Glucocorticoids; D010713:Phosphatidylcholines; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D013970:Thyronines; D014284:Triiodothyronine; C022861:3,5-dimethyl-3'-isopropyl-L-thyronine; D003907:Dexamethasone