Regulation of surfactant protein D expression by glucocorticoids in vitro and in vivo.
SP-D is a recently described lung-associated protein that is produced by alveolar type II cells and may function in pulmonary host defenses. Since little is known regarding the hormonal regulation of SP-D, and since the other surfactant proteins (SP-A, SP-B, and SP-C) are known to be regulated by glucocorticoids, we sought to determine the effects of glucocorticoids on SP-D mRNA and protein expression, both in vitro and in vivo, in the fetal rat lung. In vitro experiments were performed on lung explants from fetuses on gestational day 15 or 18. Explants were cultured in serum-free conditions with or without hydrocortisone for 3 days. SP-D mRNA expression was evaluated by Northern blot analysis. SP-D protein expression was analyzed using a polyclonal antibody against SP-D and standard immunohistochemical techniques. The expression of SP-D mRNA increased in fetal day 15 explants but remained unchanged in fetal day 18 explants cultured without the addition of hydrocortisone, compared with in vivo controls. The addition of hydrocortisone resulted in increases in SP-D mRNA expression at both gestational ages. This pattern of SP-D mRNA expression was compared with the expression of the other surfactant proteins and found to be most similar to that of SP-B. In vivo experiments were performed using maternal administration of dexamethasone (1 mg/kg) or an equal volume of saline on fetal days 15, 16, and 17 or on fetal day 17 with sacrifice on fetal day 18.(ABSTRACT TRUNCATED AT 250 WORDS)
Deterding
R R
RR
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Shimizu
H
H
Fisher
J H
JH
Shannon
J M
JM
D000818:Animals; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D006854:Hydrocortisone / Q000502:physiology*; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D006023:Glycoproteins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003907:Dexamethasone; D006854:Hydrocortisone