Fetal androgen exposure inhibits fetal rat lung fibroblast lipid uptake and release

Fetal lung fibroblasts provide lipid substrate for the II cell surfactant p hospholipid synthesis. This process is developmental and glucocorticoid dep endent. Previous studies in our laboratory demonstrating sex differences in several aspects of lung maturation suggest that these differences may be d ue to effects of fetal androgens. Based on these studies, we hypothesi;ed t hat fetal lung fibroblast triglyceride metabolism is determined by opposing effects of fetal androgens and glucocorticoids. To model the effects of an drogens on fetal lung fibroblast triglyceride metabolism, pregnant rats wer e treated with dihyrdrotestosterone (DHT) 1 mg/kg/day from the days 15 to 2 0 of gestation and changes in triglyceride content of freshly isolated feta l rat lung fibroblasts (FRLF) and rates of uptake and prostaglandin E-2 (PG E(2))-mediated release by cultured FRLF in response to glucocorticoids in t he presence or absence of DHT In vitro were measured. During lung developme nt, the triglyceride content and rate of uptake of female-derived FRLF incr eased 3.5- and 4.8-fold, respectively, between days 18 and 20 of gestation. From days 19 to 22, male FRLF trigyclyceride content and rate of uptake we re lower than the content and uptake by female FRLF. Maternal DHT treatment inhibited the normal developmental increase in fibroblast triglyceride con tent and rate of uptake between days 19 and 22 by both male and female FRLF . In. the absence of maternal DHT, in vitro dexamethasone stimulated trigly ceride uptake 3-fold by day 21 in FRLF. This effect was blocked by maternal preteatment with DHT Maternal DHT exposure prevented stimulation of trigly ceride release by PGE(2). Although in vitro dexamethasone stimulated trigly ceride release by maternal DHT-exposed fibroblasts, it did not enhance the response to PGE(2). These data suggest that in utero exposure to androgens (1) delay the developmental increase in triglyceride content and (2) oppose the effects of glucocorticoid on cultured FRLF triglyceride uptake and PGE (2)-mediated release.