TRIIODOTHYRONINE MODULATES GROWTH, SECRETORY FUNCTION AND ANDROGEN RECEPTOR CONCENTRATION IN THE PROSTATIC-CARCINOMA CELL-LINE LNCAP

There is increasing evidence that the course of prostatic carcinoma is determined by a complex interplay between genetic events, paracrine i nteractions, and hormonal and dietary factors. These latter factors in clude several ligands of the nuclear receptor family such as androgens , vitamin D-3 and retinoids. To test whether thyroid hormones also inf luence the growth and differentiated function of prostatic carcinoma c ells, LNCaP cells were treated with or without triiodothyronine (T-3) in the absence or in the presence of other regulatory factors. Exposur e of LNCaP cells to T-3 for 6 days in the absence of androgens caused a dose-dependent increase in [H-3]-thymidine incorporation with a maxi mal stimulation of 2.5-fold at 10(-9) M T-3 Secretion of prostate-spec ific antigen (PSA) was also stimulated 2-3-fold. The observed effects may well be mediated by a nuclear Tg receptor as evidenced by displace able T-3 binding studies. Combined treatment of LNCaP cells with andro gens and T-3 revealed intriguing interactions between these two pathwa ys. Below and up to 10(-10) M of the synthetic androgen R1881, the con centration that evokes optimal proliferative responses, T-3 stimulated [H-3]thymidine incorporation. At higher concentrations of androgens, T-3 displayed antiproliferative effects. No androgen-dependent effects on T-3 receptor levels were observed. Conversely, T-3 increased andro gen receptor levels up to twofold. Androgen as well as T-3 stimulation of proliferation was abolished by high concentrations of the retinoid 9-cis-retinoic acid. These data add T-3 to the list of factors that i nfluence growth and differentiation of prostatic tumor cells and contr ibute to our understanding of the intricate pathways that ultimately d etermine the course of prostatic carcinoma.