TRANSFORMING-GROWTH-FACTOR-BETA-1 BINDING AND RECEPTOR KINETICS IN FETAL MOUSE LUNG FIBROBLASTS

TGF beta 1 inhibits fetal lung maturation in vitro, As TGF beta 1 is p resent in fetal lung, mechanisms must exist to overcome this inhibitio n and allow late gestation maturation to progress, We studied the onto geny of TGF beta 1 binding, and TGF beta receptor kinetics and subtype s in primary cultures of fetal mouse lung fibroblasts from Day 16 to D ay 18 of gestation. TGF beta 1 specific binding in fetal lung fibrobla sts declined with advancing gestation, The decrease occurred earlier, and was more pronounced in female fibroblasts (50% decrease) than in t he male fibroblasts (29% decrease). Dihydrotestosterone treatment of D ay 18 female fibroblasts resulted in a dose-dependent increase in TGF beta 1 binding, Scatchard analysis revealed a decline in receptor numb er with advancing gestation (Day 16 female B-max: 7.3 x 10(-16) Day 18 female B-max: 5.5 x 10(-16)) whereas binding affinities remained cons tant. Affinity labeling followed by chemical cross-linking and autorad iography showed the three known TGF beta receptor subtypes at both Day s 16 and 18 of gestation. The relative abundance of nonsignaling Type III receptors in comparison to signaling Type II and Type I receptors was increased at Day 18 versus Day 16, Incorporation of [H-3]thymidine into DNA lifter treatment with TGF beta 1 changed from Day 16 to Day 18, consistent with changes previously reported between fetal and adul t lung fibroblasts. We conclude that a!; fetal mouse lung maturation p rogresses, TGF beta receptor number decreases in fibroblasts, the rela tive proportion of nonsignaling versus signaling receptor types increa ses, and the response to TGF beta 1 stimulation changes, These changes may contribute! to overcoming TGF beta 1 inhibition of lung maturatio n.