Development of fibroblast-type-II cell communications in fetal rabbit lung organ culture.
The development of the fetal lung is regulated by fibroblast-type-II cell communications which involve fibroblast pneumonocyte factor (FPF). FPF production is positively regulated by glucocorticoids and negatively regulated by dihydrotestosterone (DHT) and transforming growth-factor beta (TGF-beta). We studied whether DHT or TGF-beta affected other steps in the process of lung maturation, by studying how the developing lung in organ culture would respond to exogenously supplied FPF after DHT or TGF-beta exposure. Fetal rabbit (day 19 of gestation) lung organ cultures were prepared and cultured in the presence of cortisol, DHT or TGF-beta. After seven days, the media were replaced with serum-free medium containing either cortisol or FPF conditioned medium. The incorporation of [14C]glycerol into surfactant lamellar body DSPC was studied over 24 h as the index of surfactant synthesis. Results were compared to simultaneous control cultures. Treatment had no significant effect on tissue protein concentration or on the efficiency of lamellar body recovery. Cortisol stimulated baseline incorporation of glycerol into DSPC. This was inhibited by DHT, such that DHT plus cortisol treatment was no different from untreated controls. FPF stimulated the incorporation of glycerol into DSPC, and did so even after culture treatment with DHT. Cultures treated with TGF-beta exhibited glycerol incorporation similar to untreated controls. After TGF-beta exposure, FPF did not stimulate glycerol incorporation into DSPC. We conclude that DHT interferes with progression of lung development by delaying the appearance of FPF production by the fibroblast. TGF-beta, on the other hand, inhibits other elements of lung maturation besides FPF production. We speculate that TGF-beta interferes with type-II cell development such that the cell cannot respond to FPF.
Nielsen
H C
HC
Department of Pediatrics, New England Medical Center, Boston, MA 02111.
Kellogg
C K
CK
Doyle
C A
CA
D000818:Animals; D002450:Cell Communication; D013196:Dihydrotestosterone / Q000494:pharmacology; D005333:Fetus / Q000166:cytology / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008954:Models, Biological; D009924:Organ Culture Techniques; D010713:Phosphatidylcholines / Q000032:analysis; D011663:Pulmonary Surfactants / Q000032:analysis; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005938:Glucocorticoids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D016212:Transforming Growth Factor beta; C044220:fibroblast pneumonocyte factor; D013196:Dihydrotestosterone; D005346:Fibroblast Growth Factors