Type 1 deiodinase is stimulated by iodothyronines and involved in thyroid hormone metabolism in human somatomammotroph GX cells

Background: Local 5'-deiodination of L-thyroxine (T-4) to the active thyroi d hormone, 3,3',5-tri-iodothyronine (T-3) via two deiodinase isoenzymes (D1 and D2) has an important role for various T-3-dependent functions in the a nterior pituitary. However. no evidence has been presented yet for thyroid hormone inactivation via the 5-deiodinase (D3) in anterior pituitary models . Methods: Using the human somatomammotroph cell line, GX, we analysed effect s of T-3 and its 5'-deiodination product, 3,5-di-iodothyronine (3,5-T-2), o n deiodinase activities, measuring release of iodide-125 (I-125(-)) from ph enolic-ring- or tyrosyl-ring-labelled substrates respectively. Results: T-3 and 3,5-T-2 rapidly stimulated D1 activity in GX cells in the presence of serum in the culture medium, whereas D2 activity was not detect able under these conditions. However, when the cells were kept under serum- free conditions, specific activity of D2 reached levels similar to those of D1, With tyrosyl-ring labelled 3,5-[I-125]-,3'-T-3 as substrate, a signifi cant release of I-125(-) was observed in GX cell homogenates. This is compa rable to the D1 activity of liver membranes, which preferentially catalyses 5'-deiodination, but to some extent also 5-deiodination, at the tyrosyl ri ng. Conclusions: D1 activity of human GX cells is increased by T-3 and 3,5-T-2, Inactivation of T-3 in the anterior pituitary might occur by deiodination at the tyrosyl ring via D1, thus terminating the stimulatory thyroid hormon e signal in human somatomammotroph cells.