Unliganded estrogen receptor-alpha activates transcription of the mammary gland Na+/I- symporter gene.

The function of sodium iodide symporter (Na(+)/I(-) symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I(-) in milk; the newborn's first source of I(-) for thyroid hormone synthesis. Furthermore, increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS.