Esquenet M, Swinnen J V, Heyns W, Verhoeven G
Department of Developmental Biology, Catholic University of Leuven, Belgium.
Mol Cell Endocrinol. 1995 Mar;109(1):105-11. doi: 10.1016/0303-7207(95)03490-x.
There is increasing evidence that the course of prostatic carcinoma is determined by a complex interplay between genetic events, paracrine interactions, and hormonal and dietary factors. These latter factors include several ligands of the nuclear receptor family such as androgens, vitamin D3 and retinoids. To test whether thyroid hormones also influence the growth and differentiated function of prostatic carcinoma cells, LNCaP cells were treated with or without triiodothyronine (T3) in the absence or in the presence of other regulatory factors. Exposure of LNCaP cells to T3 for 6 days in the absence of androgens caused a dose-dependent increase in [3H]-thymidine incorporation with a maximal stimulation of 2.5-fold at 10(-9) M T3. Secretion of prostate-specific antigen (PSA) was also stimulated 2-3-fold. The observed effects may well be mediated by a nuclear T3 receptor as evidenced by displaceable T3 binding studies. Combined treatment of LNCaP cells with androgens and T3 revealed intriguing interactions between these two pathways. Below and up to 10(-10) M of the synthetic androgen R1881, the concentration that evokes optimal proliferative responses, T3 stimulated [3H] thymidine incorporation. At higher concentrations of androgens, T3 displayed antiproliferative effects. No androgen-dependent effects on T3 receptor levels were observed. Conversely, T3 increased androgen receptor levels up to twofold. Androgen as well as T3 stimulation of proliferation was abolished by high concentrations of the retinoid 9-cis-retinoic acid. These data add T3 to the list of factors that influence growth and differentiation of prostatic tumor cells and contribute to our understanding of the intricate pathways that ultimately determine the course of prostatic carcinoma.
越来越多的证据表明，前列腺癌的病程由基因事件、旁分泌相互作用以及激素和饮食因素之间的复杂相互作用所决定。后一类因素包括核受体家族的几种配体，如雄激素、维生素D3和视黄酸。为了测试甲状腺激素是否也影响前列腺癌细胞的生长和分化功能，在有或没有其他调节因子的情况下，用或不用三碘甲状腺原氨酸（T3）处理LNCaP细胞。在没有雄激素的情况下，将LNCaP细胞暴露于T3 6天会导致[3H]-胸腺嘧啶核苷掺入量呈剂量依赖性增加，在10(-9) M T3时最大刺激为2.5倍。前列腺特异性抗原（PSA）的分泌也被刺激了2至3倍。可置换的T3结合研究证明，观察到的效应很可能由核T3受体介导。用雄激素和T3联合处理LNCaP细胞揭示了这两条途径之间有趣的相互作用。在合成雄激素R1881达到并低于10(-10) M（即引起最佳增殖反应的浓度）时，T3刺激[3H]胸腺嘧啶核苷掺入。在雄激素浓度较高时，T3表现出抗增殖作用。未观察到雄激素对T3受体水平的依赖性效应。相反，T3使雄激素受体水平增加了两倍。高浓度的类视黄醇9-顺式视黄酸消除了雄激素以及T3对增殖的刺激。这些数据将T3添加到影响前列腺肿瘤细胞生长和分化的因素列表中，并有助于我们理解最终决定前列腺癌病程的复杂途径。
