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We previously found that glucocorticoid treatment of pregnant sheep increases the content of surfactant proteins SP-A and SP-B in lung tissue and lavage of preterm lambs. To investigate the

mechanism of this induction process, we quantitated SP mRNA levels after administration of betamethasone(0.5 mg/kg) to pregnant sheep prior to premature delivery of the fetus at 125 days. In

the first protocol, 55 sheep were injected weekly with 1-4 doses of either saline (control) or betamethasone beginning at 104 days gestation with the last dose given 24 h prior to delivery.

In a second protocol, 39 sheep were injected with 1-2 doses of saline or betamethasone at 24 and 48 h prior to delivery. Total RNA was extracted from fetal lung and hybridized with cDNAs

for sheep SP-A, SP-B and SP-C and human β-actin. mRNA levels for control preterm lambs were 21%, 28% and 39% of the level in term lambs for SP-A, -B and -C, respectively. No increases in

mRNA levels were demonstrated in sheep given 1-3 weekly doses of betamethasone vs. control. However, 4 doses of betamethasone, as well as both 48h treatment regimens, produced a 2- to 3-fold

increase in each SP mRNA (p<0.01 by ANOVA), achieving levels equivalent to 60-75% of term control lambs. The magnitude of the betamethasone-induced increase in SP mRNA is similar to that

for tissue SP-A and SP-B after 2-4 betamethasone doses. The observation that SP-A and SP-B proteins are increased 2 wk after betamethasone treatment, whereas mRNAs are not, implies that

induction occurs with 2 doses, is reversible, and that the proteins have a longer half-life than the mRNAs. We conclude that _in vivo_ betamethasone treatment rapidly induces a maximal and

coordinated increase in SP-A, SP-B, and SP-C mRNAs which is fully reversible within 7 days. Similar increases in SP mRNA and protein content confirm that glucocorticoid regulation of SP

genes _in vivo_ is largely transcriptional. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Depts. of Peds., U. Penn., Children's Hosp., Philadelphia, PA R C Tan, J Gonzales, M S Strayer,

 P L Ballard, M Ikegami, A H Jobe & F Possmayer * Children's Hosp., Cincinnati, OH R C Tan, J Gonzales, M S Strayer, P L Ballard, M Ikegami, A H Jobe & F Possmayer * Univ. of

Western Ontario, London, ON R C Tan, J Gonzales, M S Strayer, P L Ballard, M Ikegami, A H Jobe & F Possmayer Authors * R C Tan View author publications You can also search for this

author inPubMed Google Scholar * J Gonzales View author publications You can also search for this author inPubMed Google Scholar * M S Strayer View author publications You can also search

for this author inPubMed Google Scholar * P L Ballard View author publications You can also search for this author inPubMed Google Scholar * M Ikegami View author publications You can also

search for this author inPubMed Google Scholar * A H Jobe View author publications You can also search for this author inPubMed Google Scholar * F Possmayer View author publications You can

also search for this author inPubMed Google Scholar ADDITIONAL INFORMATION (Spon by: Philip L. Ballard) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

Tan, R., Gonzales, J., Strayer, M. _et al._ Developmental and Glucocorticoid Regulation of Surfactant Protein mRNAs in Fetal Sheep † 310. _Pediatr Res_ 43 (Suppl 4), 55 (1998).

https://doi.org/10.1203/00006450-199804001-00331 Download citation * Issue Date: 01 April 1998 * DOI: https://doi.org/10.1203/00006450-199804001-00331 SHARE THIS ARTICLE Anyone you share the

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