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 (T4) to the active thyroid hormone, 3,3',5-tri-iodothyronine (T3) via two deiodinase isoenzymes (D1 and D2) has an important role for various T3-dependent functions in the anterior 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 effects of T3 and its 5'-deiodination product, 3,5-di-iodothyronine (3,5-T2), on deiodinase activities, measuring release of iodide-125 (125I-) from phenolic-ring- or tyrosyl-ring-labelled substrates respectively.


RESULTS
T3 and 3,5-T2 rapidly stimulated D1 activity in GX cells in the presence of serum in the culture medium, whereas D2 activity was not detectable 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-[125I]-,3'-T3 as substrate, a significant release of 125I- was observed in GX cell homogenates. This is comparable to the D1 activity of liver membranes, which preferentially catalyses 5'-deiodination, but to some extent also 5-deiodination, at the tyrosyl ring.


CONCLUSIONS
D1 activity of human GX cells is increased by T3 and 3,5-T2. Inactivation of T3 in the anterior pituitary might occur by deiodination at the tyrosyl ring via D1, thus terminating the stimulatory thyroid hormone signal in human somatomammotroph cells.
Baur
A
A
Klinische Forschergruppe der Medizinischen Poliklinik der Universität Würzburg, RIntgenring 11, D-97070 Würzburg, Germany.
Köhrle
J
J
D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013963:Thyroid Hormones / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*; D014285:Triiodothyronine, Reverse / Q000494:pharmacology / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D013963:Thyroid Hormones; D014284:Triiodothyronine; D014443:Tyrosine; D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase