Antithyroid action of tamoxifen in the rat: in vivo and in vitro studies.
The influence of administration of tamoxifen (TAM) on thyroid metabolism was investigated. The potential action of TAM on iodine in the thyroid gland was evaluated by determination of the equilibrium constant of the charge transfer complex formed with molecular iodine and by computational studies. Adverse effects of TAM on thyroid function parameters were also investigated in female Wistar rats. Rats were treated for seven weeks with 5 mg/kg/day of TAM. Irrespective of the iodine content of the diet, administration of TAM led to goitre and a significant increase in levels of T4 and TSH. Similar results, albeit more marked, were observed after administration of an inhibitor of thyroid peroxidase. We also showed that TAM forms charge transfer complex with iodine (Kc = 876 liters/mol). We concluded that under our experimental conditions, TAM exerts antithyroid activity from an action on thyroid peroxidase. Nevertheless, when the exogenous iodine contribution is restricted, TAM may sequester iodine in the form of charge transfer complexes, thereby enhancing hypothyroidism.
Beyssen
M
M
Department of Organic and Therapeutic Chemistry, Laboratoire de Chimie des Substances Naturelles, Faculty of Pharmacy, Limoges, France.
Lagorce
J
J
Clédat
D
D
Jambut
A
A
Buxeraud
J
J
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D007455:Iodine / Q000652:urine; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013961:Thyroid Gland / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood
D013956:Antithyroid Agents; D020847:Estrogen Receptor Modulators; D013844:Thiazoles; D053778:Thiazolidines; D013963:Thyroid Hormones; D013629:Tamoxifen; C005104:2-mercaptothiazoline; D007455:Iodine