INHIBITORY EFFECT OF DIHYDROTESTOSTERONE ON HUMAN THYROID-CELL GROWTH

Sex steroid-binding activities have been identified by several authors in normal and pathological thyroids and the expression of the canonic androgen receptor (AR) has recently been demonstrated in human thyroi d follicular cells. In order to assess what influence, if any, androge n exposure has on thyroid cell growth, the effect of dihydrotestostero ne (DHT) on [H-3]thymidine (thy) incorporation and cell proliferation was investigated in thyroid follicular cells in vitro. In a primary cu lture of goitrous cells, DHT induced a significant reduction of[H-3]th y incorporation at concentrations ranging from 10(-12) to 10(-8) M, wi th a more pronounced effect at 10(-9) M. At this concentration, the in hibitory effect was evident after both 24 and 48 h of treatment and in Various types of primary thyroid cell cultures. In goitrous cells, th e DHT-induced decrease of [H-3]thy was associated with a reduction of expression of the proliferation-associated nuclear Ki-67 antigen, a pr otein commonly used to assess cell growth fraction. In TPC cells, an A R-positive thyroid papillary carcinoma cell line, DHT at concentration s between 10(-12) and 10(-8) M significantly decreased the growth rate . DHT (10(-9) M) produced an approximately 50-60% inhibition of cell p roliferation and the antiandrogen cyproterone acetate was capable of r eversing such effects. The DHT-induced reduction of TPC cell prolifera tion was associated with a significant reduction of c-myc RNA levels. Thyroperoxidase mRNA levels and thyroglobulin production were not redu ced by androgen in primary cultures of goitrous cells. In conclusion, our results indicated that androgens may have a role in this gland by reducing the proliferation, but not the function, of follicular cells.