The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin

Abstract

The pyrethroids are a class of natural and synthetic pesticides which were associated with an epidemic of gynecomastia in Haitian men in 1981. In the present study we tested several pyrethroids for their ability to interact with androgen binding sites in dispersed, intact human genital skin fibroblasts and in human plasma to sex hormone binding globulin (SHBG). All the pyrethroids tested inhibited fibroblast binding of [ 3H]methyltrienolone (R1881) at 22°C with the following rank order of potency : pyrethrins > bioallethrin > fenvalerate > fenothrin > fluvalinate > permethrin > resmethrin. 50% displacement of [ 3H]R1881 binding to fibroblast androgen receptors was achieved by 1.5–44 × 10 −5M concentrations of the competitors, respectively. Previous studies with cimetidine, a known inhibitor of androgen receptor binding, showed 50% competition at a concentration of 1.4 × 10 −4M in this system. Scatchard analysis of binding experiments performed with increasing concentrations of [ 3H]R1881 in the presence of the pyrethroids indicated that the binding inhibition was competitive. On the other hand, of the pyrethroids examined only the pyrethrins (50% inhibition) and bioallethrin (43% inhibition) were able to displace [ 3H]testosterone from SHBG when tested at a concentration of 10 −4 M. These data indicate that a novel class of non-steroidal compounds, the pyrethroids, can interact competitively with human androgen receptors and SHBG. These findings provide a mechanism by which chronic exposure of humans or animals to pesticides containing these compounds may result in disturbances in endocrine effects relating to androgen action.