Testosterone and estradiol have specific differential modulatory effect on the proliferation of human thyroid papillary and follicular carcinoma cell lines independent of TSH action
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.
Key WordsTestosterone estradiol thyroid carcinoma proliferation androgen receptor estrogen receptor TSH receptor flutamide tamoxifen
Unable to display preview. Download preview PDF.
- 1.LiVolsi VA. Pathology. In: Braverman LE, Utiger RD, eds. The thyroid. Philadelphia, PA: Lippincott-Raven, 1996; 497.Google Scholar
- 2.Pacini F, De Groot LJ. Thyroid neoplasia. In: De Groot LJ, Jameson JL, eds. Endocrinology, IV edition, Vol. II. Philadelphia, PA: W.B. Saunders, 2001; 1541–1566.Google Scholar
- 4.Paloyan E, Hoffmann C, Prinz RA. Castration induces a marked reduction in the incidence of thyroid cancers. Surgery 92:834–848, 1982.Google Scholar
- 6.Zielke A, Hofmann S, Planl U, Duh Q-Y, Clark OH, Rothmund M. Pleotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion. Exp Clin Endocrinol Diab 107:361–369, 1999.CrossRefGoogle Scholar
- 7.Sheridan PJ, McGill HC, Jean J, Lissitzky C, Martin PM. The primate thyroid gland contains receptors for androgens. Endocrinology 115:2690–2693, 1984.Google Scholar
- 11.Morgan SJ, Darling DC. Culturing continuous cell lines. In: Graham JM, Billington D, eds. Animal cell culture. Oxford: BIOS Scientific, 1993; 37–50.Google Scholar
- 12.Yu M, Lin JD, Giuliano AE, Juillard GJF, van Here KAM, Van Herle AJ. Estrogen and progesterone receptor expression and E-2 regulated cell proliferation in four human thyroid cancer cell lines. Thyroidol Clin Exp 8:79–86, 1996.Google Scholar
- 17.Gross C, Yu M, Van Herle AJ, Giuliano AE, Juillard GJ. Presence of a specific antiestrogen binding site on human follicular thyroid carcinoma cell line (UCLA RO 82 W-1): inhibition by an endogenous ligand present in human serum. J Clin Endocrinol Metab 77:1361–1366, 1993.PubMedCrossRefGoogle Scholar
- 21.Rapoport B, Spaulding SW. Mechanism of action of thyrotropin and other thyroid growth factors. In: Braverman LE, Utiger RD, eds. The thyroid. Philadelphia, PA: Lippincott-Raven, 1996; 207–219.Google Scholar