Role of TSH in the Spontaneous Development of Asymmetrical Thyroid Carcinoma in Mice with a Targeted Mutation in a Single Allele of the Thyroid Hormone B Receptor

ZHAO LI; ZHU XUGUANG; PARK JEONG WON; FOZZATTI LAURA; WILLINGHAM MARK C; CHENG SHEUE-YANN

ENDOCRINE SOC

Año: 2012

utations of the thyroid hormone receptor- gene (THRB) cause resistance to thyroid hormone (RTH).Amouse model of RTH harboring a homozygous thyroid hormone receptor (TR)- mutation known as PV (ThrbPV/PV mouse) spontaneously develops follicular thyroid cancer (FTC). Similar to RTHpatients with mutations oftwoalleles of theTHRBgene, the ThrbPV/PVmouseexhibits elevated thyroid hormones accompanied by highly nonsuppressible TSH. However, the heterozygous ThrbPV/ mouse with mildly elevated TSH (2-fold) does not develop FTC. The present study examined whether the mutation of a single allele of the Thrb gene is sufficient to induce FTC in ThrbPV/ mice under stimulation by high TSH. ThrbPV/ mice and wild-type siblings were treated with propylthiouracil (PTU) to elevate serum TSH. ThrbPV/mice treated with PTU (ThrbPV/-PTU) spontaneously developed FTC similar to human thyroid cancer, but wild-type siblings treated withPTU did not. Interestingly, approximately 33% of ThrbPV/-PTU mice develo