DIRECT PHARMACOLOGIC EFFECTS OF DHT ON THE ALVEOLAR TYPE II CELL IN VITRO

Abstract

Previous studies from our laboratory have demonstrated that dihydrotestosterone (DHT) inhibits the production of pulmonary surfactant in vivo and its de novo synthesis in tissue culture (J. Cell Biology, 97, 86a, 1983). Studies in tissue culture suggest that DHT has no effect on the fibroblast-type II cell interaction which gives rise to surfactant, but blocks this mechanism in response to cortisol at very low doses (≤ 10−8M) comparable to the circulating level of androgens in the fetus and to the Kd of the androgen receptor. More recent studies suggest that 10−7M to 10−5M DHT stimulates the growth of the fetal type II cell by 40-100% while reducing the synthesis of saturated phosphatidylcholine in a reciprocal manner. These results may explain the observed in vivo effects of DHT initially on the female fetuses (10−8M) and at pharmacologic levels on both sexes at serum androgen levels at an order of magnitude greater. We conclude that the native sex difference in pulmonary surfactant production is due to the effects of androgen on mesenchymal-epithelial interactions, but that DHT may have direct, pharmacologic effects on type II cell maturation as well. (Supported by NIH Grant #HL28315-02).