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Development and characterization of a variant GC cell line with L-triiodothyronine-independent growth and growth hormone production.

To facilitate studies of cell growth regulation by T3, we developed a variant GC cell line (V-GC) characterized by normal growth in T3-depleted (-T3) medium. The doubling time (dt) of V-GC cells was 28.8 h (-T3) and 28.0 h (+0.2 nM T3), respectively, whereas the dt of the parent GC cells, 24.0 h (+0.2 nM T3), increased to more than 100 h (-T3). The dt of V-GC cell was unaffected even by maximal T3 (5 nM). Cell protein (micrograms) per microgram DNA increased in GC cells in a T3 concentration-dependent manner, whereas V-GC cell protein was unaffected by T3. GH production appeared partially independent of T3 in V-GC cells. GH production (nanograms per 10(6)/h) in V-GC cells maintained for 3 months in -T3 medium was 3.3- to 4.6-fold greater than that in GC cells after 4 days in -T3 medium (P less than 0.001). Addition of T3 resulted in similar maximal GH production in both cell lines. The binding capacity and Ka of nuclear T3 receptors were similar in GC and V-GC cultures, and receptor down-regulation in response to added T3 occurred similarly in both cultures. Lastly, studies employing conditioned medium indicated that T3-independent growth of V-GC cells did not result from production of an autocrine growth factor. Our findings raise the possibility that overexpression of a transacting cell-specific gene-regulating protein that variably affects thyroid hormone-dependent genes may account for the phenotype of the V-GC cultures.