Dexamethasone-resistant cystic fibrosis fibroblasts show cross-resistance to sex steroids.

Diploid skin fibroblasts derived from individuals with the autosomal recessive disease, cystic 
fibrosis (CF), were shown previously to be significantly more resistant to 
the cytotoxicity of dexamethasone, a glucocorticoid hormone, than were normal human 
fibroblasts. Here cystic fibrosis fibroblasts are also shown to be more 
resistant than normal human fibroblasts to the cytotoxic effects of the 
sex hormones, 17 beta-estradiol, dihydrotestosterone and progesterone. Since cells are believed 
to contain different receptors for each of the steroid hormones, it 
is not probable than the resistance of CF cells to these 
hormones results from a receptor deficiency. This was shown by the 
fact that CF cells were found to exhibit the same receptor 
activity as normal cells for 3-H-dexamethasone. Furthermore, neither normal human nor 
CF fibroblasts could be demonstrated to contain detectable receptor activity for 
3H-17 beta-estradiol. In addition, the studies of fibroblast killing by hormones 
led to the further interesting observation that normal human diploid fibroblasts, 
regardless of the sex of the tissue donor, are sensitive to 
killing by each of the sex hormones. These findings suggest that 
the cytotoxic effects of the steroid hormones may be observed independently 
of the specific hormone receptors. The studies reported here thus suggest 
that the resistance of CF cells to the different steroid hormones 
is probably the result of a defect in a pathway in 
cellular steroid hormone metabolism other than that involving receptors. 