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 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.
Esquenet
M
M
Department of Developmental Biology, Catholic University of Leuven, Belgium.
Swinnen
J V
JV
Heyns
W
W
Verhoeven
G
G
D000728:Androgens / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D011944:Receptors, Androgen; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D015741:Metribolone; D014212:Tretinoin; D017430:Prostate-Specific Antigen