Induction of amino acid transport by L-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells (GC cells)

The action of L-triiodothyronine (T₃) on amino acid transport in the GC clonal strain of rat pituitary cells was investigated by measurement of the uptake of the nonmetabolizable amino acid, α-aminoisobutyric acid (AIB). The uptake of AIB by GC cells appeared to require energy and Na⁺ and displayed Michaelis-Menten kinetics. In comparison to cultures maintained in the absence of T₃, T₃ addition resulted in an increase in AIB uptake which seemed due to an increase in the initial rate of AIB transport. T₃ addition resulted in increased AIB accumulation at later time points as well. T₃ induction of AIB transport did not occur until 3.5 h after addition of T₃, and this effect was blocked by cycloheximide. Maximal induction occurred 48 to 72 h later. One-half maximal induction occurred 24 to 48 h after addition of T₃. No detectable changes either in AIB uptake or intracellular water space, measured by uptake of the nonmetabolizable sugar, 3-O-methyl-D-glucose, were noted for the first 120 min after addition of T₃. Induction of AIB transport occurred at 0.05 nM T₃ (total medium concentration) and one-half maximal induction occurred at 0.17 nM T₃. The relative potencies of four iodothyronine analogues for AIB transport were in accord with their reported activities in nuclear T₃ receptor binding assays. These data suggest that induction of AIB transport by T₃ may be mediated by the nuclear T₃ receptor and may reflect the pleiotrophic response of GC cells to thyroid hormone.