Estradiol Regulates the Expression of Type 3 Deiodinase in a Chondrocyte Cell Line

Although accelerated growth is observed in both sexes upon reaching puberty, the growth of girls ceases around menarche (the average age at menarche is 12-13 years in Japan). However, the molecular basis of the action of estrogen remains unclear. In this study, we investigated whether estrogen is involved in the differences in growth between males and females while focusing on thyroid hormone metabolic enzymes. We analyzed the promoters of iodothyronine deiodinase (DIO)2 and DIO3 by 17β-estradiol (E₂). ATDC5 cells (mouse chondrocytes cell line) were treated with E₂, and the expression of DIO2 and DIO3 mRNA and proteins was evaluated. Sham-operated (sham) or ovariectomized (OVX) female mice were treated daily with E₂ or vehicle for three consecutive weeks. Subsequently, the left femur was removed to evaluate the effect of E₂ on DIO2/DIO3 gene and protein expression. E₂ increased the transcriptional activity of DIO3 in a concentration-dependent manner. On the DIO3 promoter indicates the presence of an estrogen response element. DIO2 and DIO3 mRNA and protein expression in ATDC5 cells in the presence of E₂ was significantly increased, while DIO2 expression was unchanged. In vivo, we used OVX mice and E₂ supplementation as a model of amenorrhea for further investigation. DIO3 expression was significantly increased in mice treated with E₂ in OVX compared to that in mice treated with vehicle in sham. E₂ increases DIO3 expression in chondrocytes and long bone tissues, suggesting that E₂ may affect bone growth and cause sexual dimorphism during puberty.