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Hormonal Regulation of Radioiodide Uptake Activity and Na⁺/I^- Symporter Expression in Mammary Glands¹

Departments of Physiology and Cell Biology (J.-Y.C., R.K., E.L.M., S.M.J.), Surgery (W.E.B.), College of Medicine, and Veterinary Clinical Sciences (R.L.), Ohio State University, Columbus, Ohio 43210; INSERM, Faculté de Médecine Lyon-RTH Laennec (B.R.), 69372 Lyon, France; and National Hormone and Pituitary Program, Harbor-University of California Medical Center Research and Education Institute (A.F.P.), Torrance, California 90502

Address all correspondence and requests for reprints to: Sissy M. Jhiang, Ph.D., Department of Physiology and Cell Biology, Ohio State University, 302 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210-1218. E-mail: jhiang.1{at}osu.edu

The observation that radioiodide uptake (RAIU) activity, mediated by the Na⁺/I^- symporter (NIS), is significantly increased in lactating breast suggests that RAIU and NIS expression in mammary gland are modulated by hormones involved in active lactation. We showed that both the NIS expression level and RAIU in rat mammary gland are maximal during active lactation compared to those in the mammary glands of virgin and pregnant rats as well as the involuting mammary gland. In the lactating mammary gland, NIS is clustered on the basolateral membrane of alveolar cells as a lesser glycosylated form than NIS in thyroid. The RAIU of lactating mammary gland was partially inhibited by treatment with a selective oxytocin antagonist or bromocriptine, an inhibitor of PRL release. These findings suggest that RAIU and NIS expression in mammary gland are at least in part modulated by oxytocin and PRL. Indeed, we showed that NIS messenger ribonucleic acid level was increased in a dose-dependent manner by oxytocin and PRL in histocultured human breast tumors.

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