Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity

Abstract

The effects of the tri-iodothyronine (T 3 ) secreted by thyroid cells on the growth of the thyrocyte are poorly known. In this study we analyzed the effects of T 3 on the proliferation of bovine thyroid follicles in primary culture previously depleted of endogenous T 3 . Cellular deoxiribonucleic acid (DNA) synthesis, determined by [ 3 H]thymidine incorporation, was stimulated by T 3 (0·1-5·0 nM) for 24 h in a concentration-dependent fashion with a maximal effect at 1·0 nM T 3 (P<0·01). This T 3 action was time-dependent when assayed from 12 to 72 h. The induction of mitogenic activity was corroborated by the increase in proliferating cell nuclear antigen (PCNA) measured by Western blot analysis. PCNA increased after treatment with T 3 (0·1-5·0 nM) in a concentrationdependent manner. Since T 3 modifies the activity of growth factors whose actions are mainly mediated by tyrosine kinase (TK) activation in diverse cellular types, we assayed the effects of genistein, a general TK inhibitor, and tyrphostin A25, a specific epidermal growth factor (EGF)-receptor (EGFR)-dependent TK activity inhibitor, on the proliferative effects of T 3 . The T 3 -induced [ 3 H]thymidine incorporation was inhibited by both agents in a concentration-dependent manner. A significant increase in the total TK activity measured in cellular protein extracts was induced by 0·5 and 1·0 nM T 3 (P<0·001). Tyrosine phosphorylation of the EGFR was also stimulated by T 3 (P<0·001) with no change in the EGFR expression as determined by Western blot analysis. Both, the T 3 -stimulated [3 H]thymidine incorporation and the TK activity were inhibited by a anti-mouse EGF antibody. These results lead us to propose that T 3 could operate as a proliferative agent in bovine thyroid cells through a mechanism involving an autocrine/paracrine EGF/EGFR-dependent regulation.

Histometric and biochemical properties of the thyroid gland in sheep with high iodine supplementation

“…According to Shan et al (2009), the height of the follicular cells is an objective indicator of the thyroid gland activity. Lower proliferative activity of thyrocytes (presented in ewes by the level of PCNA) is according to Di Fulvio et al (2000) a sign of lower activity of the thyroid gland. This fact was confirmed by correlation between count of PCNA positive cells and percentage of large or small follicles and other correlations.…”

Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434

“…T 3 is considered a primary liver mitogen (Francavilla et al, 1994;Malik et al, 2003). It also accelerates wound healing of the skin (Safer et al, 2005), induces proliferation of cultured bovine thyroid cells (Di Fulvio et al, 2000), of bone marrow pro-B cells (Foster et al, 1999), of pancreatic acinar cells (Ohmura et al, 1997;Ledda-Columbano et al, 2006) of human insulinoma cells (Verga Falzacappa et al, 2006), and of renal proximal tubular epithelial cells (Ohmura et al, 1997). Finally, it increases DNA synthesis in osteoblasts (Kassem et al, 1993).…”

Thyroid Hormones and Growth in Health and Disease - Review

“…Animal studies have demonstrated that T3 is a liver mitogen and promotes proliferation of hepatocytes, if given after partial hepatectomy and, its effect depends on the type and developmental state of the cell (7,8). T3 also has positive effects on wound healing and on proliferation of cells, including cultured bovine thyroid cells, bone marrow pro-B cells, pancreatic acinar cells and renal proximal tubular epithelial cells (9,10,11,12,13). There are indications that T3 is required for branching morphogenesis and epithelial/mesenchymal differentiation of the lungs (14).…”