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Am J Physiol Lung Cell Mol Physiol 277: L1142-L1148, 1999;
1040-0605/99 $5.00
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Vol. 277, Issue 6, L1142-L1148, December 1999

Developmental and glucocorticoid regulation of surfactant protein mRNAs in preterm lambs

Rosemarie C. Tan1, Machiko Ikegami2, Alan H. Jobe2, Li Yuan Yao3, Fred Possmayer3, and Philip L. Ballard1

1 Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; 2 Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229; and 3 Department of Obstetrics and Gynecology and Biochemistry, Lawson Research Institute, St. Joseph's Health Centre and London Health Sciences Centre, University Campus, University of Western Ontario, London, Ontario, Canada N6A 4V2

Glucocorticoid treatment increases content of surfactant protein (SP) A and SP-B in lung tissue and lavage fluid of preterm lambs. To investigate this process, we determined the ontogeny and glucocorticoid induction of SP mRNAs. In separate treatment protocols, each with its own controls, sheep were injected with betamethasone 15 h, 48 h, or weekly for 1-4 doses before preterm delivery. Using ovine SP cDNAs, we found an increase equal to or more than threefold in basal levels of all three SP mRNAs between 125 days and term. After betamethasone treatment, SP-B and SP-C mRNA levels increased by 15 h and all SP mRNAs were elevated after 24 h (>= 2-fold); mRNA levels in fetuses delivered 1-3 wk after betamethasone were not different from control. We conclude that in vivo betamethasone rapidly induces a coordinated increase in SP mRNAs, which is fully reversible within 7 days despite repetitive doses of betamethasone. Similar increases in mRNA and protein contents for SP-A and SP-B suggest that glucocorticoid regulation of these SPs in vivo is primarily pretranslational.

betamethasone; ontogeny


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