Differential effects in vivo of thyroid hormone on the expression of surfactant phospholipid, surfactant protein mRNA and antioxidant enzyme mRNA in fetal rat lung.
Antenatal administration of triiodo-L-thyronine (T3) to late gestation rats resulted in decreased lung antioxidant enzyme (AOE) activity but increased surfactant phospholipids. In fetal rat lung explant cultures, T3 decreased the expression of surfactant proteins (SP) A and B. There have been no reported studies of the simultaneous in vivo developmental influence of T3 on both pulmonary AOE and SP gene expression. We hypothesized that antenatal T3 treatment would cause differential regulation of surfactant phospholipid, SP, and AOE genes in the late gestation fetal rat. Timed pregnant rats received intramuscular injections of either T3 (7 mg/kg) or placebo on days 19 and 20 of gestation and fetuses were delivered on day 21. Fetal lung SP-A, SP-B, SP-C, and AOE mRNA levels were studied by Northern analysis. AOE mRNA levels were further quantitated by solution hybridization. Total lung phospholipids (TPL) and disaturated phosphatidylcholine (DSPC) content were quantitated by a phosphorus assay. T3 significantly increased TPL and DSPC content, and significantly decreased the expression of SP-A, SP-C, CuZnSOD, and catalase genes. Because of a crucial interplay of these factors for normal lung function at the time of birth, the molecular mechanisms by which these apparently opposing changes are accomplished warrant further investigation.
Department of Pediatrics, Floating Hospital for Children, New England Medical Center, Boston, Massachusetts 02111, USA.
S M
SM
Ramadurai
H C
HC
Nielsen
Y
Y
Chen
D
D
Hatzis
I R
IR
Sosenko
D000818:Animals; D015152:Blotting, Northern; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012269:Ribosomal Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D017931:DNA Primers; D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C041806:ribosomal protein L32; D014284:Triiodothyronine; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase