Dihydrotestosterone blocks fetal lung fibroblast-pneumonocyte factor at a pretranslational level.
Fibroblast pneumonocyte factor (FPF) synthesis by fetal rat lung fibroblasts is augmented during gestation in the presence of cortisol. The control and cortisol-augmented levels of FPF production, as determined by FPF ability to stimulate saturated phosphotidylcholine synthesis by lung epithelial Type II cells, is delayed during development in fibroblasts derived from male fetuses as compared to those derived from female fetuses. The mechanism by which this delay occurs has been addressed. Pregnant rats treated in vivo with dihydrotestosterone (DHT) showed decreased FPF activity from control or cortisol-treated fibroblasts derived from 20-day-old male or female fetuses. In vitro translated proteins of size-fractionated lung RNA from 19-day-old fibroblasts that were pretreated with DHT in vitro showed decreased FPF activity compared to nontreated samples. This decreased FPF activity was present even if the DHT-pretreated cells were stimulated with cortisol prior to RNA preparation. Using a mouse model of testicular feminization that contains no receptors for androgens showed no change in the cortisol augmented FPF activity when the fibroblasts were pretreated with DHT. These data taken together suggest that the delayed FPF production of male-derived lung fibroblasts is a physiologic process which requires androgen receptors, and the mechanism by which androgens inhibit FPF production appears to affect events occurring mainly at a pretranslational level.
Floros
J
J
Department of Pediatrics (Biological Chemistry), Harvard Medical School, Boston, Massachusetts 02115.
Nielsen
H C
HC
Torday
J S
JS
D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
D010713:Phosphatidylcholines; C044220:fibroblast pneumonocyte factor; D013196:Dihydrotestosterone; D005346:Fibroblast Growth Factors; D006854:Hydrocortisone