Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression

T-3 plays an important role in the regulation of cell growth and differenti ation. In this study, we show the interactive effects of T-3 and androgens on the growth response and expression of the prostate-specific genes, PSA ( prostate-specific antigen) and hK2 (human glandular kallikrein), in the hum an prostate cancer cell line, LNCaP. T-3 alone showed pronounced growth enh ancement in a dose-dependent fashion. However, in the presence of androgens , higher concentrations of T-3 were required to produce additional prolifer ative effects. T-3, androgens, or a combination of the two up-regulated PSA protein production in a dose-dependent fashion, but T-3 had little stimula tory effect on hK2 protein expression, regardless of the presence or absenc e of androgens. Using gene transfer assays, T-3 alone showed no effect on transcriptional a ctivation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T-3 potentiated the androgen-mediated transcription of the PSA gene but no t that of the hK2 gene. A previous study suggested that the T-3 effect on P SA protein expression was caused by an up-regulation of the androgen recept or (AR) protein by T-3. Our results contradict these. Although AR expressio n was increased by T-3 alone, Western blot analysis showed that the total c ellular AR level was not further increased by T-3 in the presence of androg ens, in comparison with cells stimulated by androgens alone. Both Western b lot analysis and a gel DNA band shift assay revealed that nuclear AR was no t increased by T-3. This study suggests that transcription factor(s) other than the AR may mediate T-3 enhancement of androgenic induction of PSA expr ession.