Inhibition of the Type 2 Iodothyronine Deiodinase Underlies the Elevated Plasma TSH Associated with Amiodarone Treatment

摘要

There is well-established evidence in many mammalian speciesfor effects of the intrauterine position (IUP) (the sex-specificpositioning of the embryo) on postnatal brain function and be-havior. We found that the IUP affects estrogen receptor (ER) ?expression in adult female rats in the ventrolateral region of thehypothalamicventromedialnucleus(vlVMH),whichisassociatedwith sexual behavior. The ER ? expression level in the vlVMH washigher in females that developed in utero between two malesiblings (2M females) than in those that developed between fe-malesiblings(2Ffemales).Wealsofoundthatthecytosinemeth-ylationstatusacrosstheER ? promoterinthevlVMHwasaffectedbytheIUP,withgreatermethylationin3Ffemales.Thesefindingsshowed a negative correlation between ER ? expression levels inthevlVMHandmethylationfrequencyintheER ? promoter.Thissuggests that genomic methylation sustains the effect of thefetal IUP on ER ? expression in the vlVMH.