Testosterone and estradiol have specific differential modulatory effect on the proliferation of human thyroid papillary and follicular carcinoma cell lines independent of TSH action

Abstract

Differential effects of testosterone and estradiol on the proliferation of human thyroid papillary (NPA-87-1) and follicular (WRO-82-1) carcinoma cell lines were assessed by [³H]-thymidine incorporation and the cell number. Cells (2.5 × 10⁵) plated in 24-well culture plates in 400 µL RPMI-1640 medium/well, under 5% CO₂ and 95% air; at 37°C were exposed to linearly increasing concentrations of human thyroid-stimulating hormone (hTSH) (1.25–640 ng/mL), testosterone (1.25–640 ng/mL), or estradiol (1.25–640 pg/mL) for 24 h. Testosterone and estradiol increased the proliferation of NPA cell line in a dose-dependent manner; flutamide (an anti-androgen) and tamoxifen (an anti-estrogen) (10⁻⁸, 10⁻⁷, 10⁻⁶, and 10⁻⁵ mol/L) effectively inhibited the testosterone and estradiol-induced cell proliferation, respectively. While flutamide inhibited the stimulatory effect of testosterone on the WRO cell line, tamoxifen augmented the inhibitory effect of estradiol. TSH did not have any effect on the proliferation of NPA or WRO cell lines, and testosterone-estradiol had no impact on TSH binding to these cells. N-ethylmalemide (5α-reductase inhibitor) (10⁻⁸–10⁻⁵ mol/L) did not modulate basal and testosterone-induced cell proliferation, indicating the direct effect of testosterone without getting converted into dihydrotestosterone (DHT). Both the cell lines tested positive for androgen and estrogen receptors and were up-regulated by the respective ligands. It is concluded that testosterone and estradiol modify the proliferation of thyroid cancer cells through homologous up-regulation of their own receptors, which is independent of TSH, and their effects may vary according to the cell type.