Androgen regulation of epidermal growth factor receptor binding activity during fetal rabbit lung development.
Fetal lung development progresses in a sex-specific manner with male fetuses exhibiting delayed maturation. Androgens, both exogenous and endogenous, inhibit while epidermal growth factor (EGF) enhances fetal lung development. We hypothesized that one mechanism responsible for the delay in male fetal lung development is an androgen-induced delay in EGF receptor binding activity. We measured EGF binding in sex-specific fetal rabbit lung plasma membranes isolated from control fetuses (days 21, 23, 25, 27, 29, and 30 of gestation) and from androgen-treated fetuses (days 21, 23, and 27 of gestation) that had been continuously exposed in vivo to exogenous 5 alpha-dihydrotestosterone from day 12 through 27 of gestation. Specific binding of EGF was significantly lower in male than in female fetal lung tissue isolated from controls at day 21 of gestation. Scatchard analysis revealed that this decrease in EGF binding was associated with decreased EGF receptor density without any significant change in affinity. Prenatal exogenous androgen treatment led to decreased EGF binding in fetal rabbit lung tissue from both sexes secondary to a decrease in EGF receptor density. These findings suggest that one mechanism responsible for the delay in male fetal lung maturation is an androgen-induced delay in EGF receptor binding activity during fetal lung development.
Klein
J M
JM
Department of Pediatrics, University of Iowa, Iowa City 52242.
Nielsen
H C
HC
D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive; D013196:Dihydrotestosterone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005325:Fetal Organ Maturity / Q000502:physiology*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011247:Pregnancy; D011817:Rabbits; D012737:Sex Factors
D000728:Androgens; D013196:Dihydrotestosterone; D004815:Epidermal Growth Factor; D066246:ErbB Receptors