Prolactin regulation of the pendrin-iodide transporter in the mammary gland

Abstract

Iodide is an essential constituent of milk that is present in concentrations more than an order of magnitude higher than in the maternal plasma. Earlier, a sodium-iodide symporter was identified in the mammary gland; this transporter is presumed to take iodide from the maternal plasma into the alveolar epithelial cells of the mammary gland. We now report the existence of a second iodide transporter, pendrin, which is also essential for iodide accumulation in milk. Via Western blotting methods, high levels of the transporter were detected in lactating tissues; lesser amounts were found in tissues from midpregnant and virgin mice. Prolactin, at physiological concentrations, stimulated the expression of the pendrin transporter in cultured mammary tissues taken from 12- to 14-day-pregnant mice. The prolactin effect on iodide uptake into cultured mammary tissues was abolished by pendrin transport inhibitors, including DIDS, furosemide, and probenecid. These studies suggest that the prolactin stimulation of pendrin activity is an essential element in the prolactin stimulation of iodide uptake into milk.

Loss of cochlear HCO3−secretion causes deafness via endolymphatic acidification and inhibition of Ca2+reabsorption in a Pendred syndrome mouse model

“…Expression has been found in the inner ear and thyroid gland consistent with the clinical manifestations of deafness and goiter (10,11,32,44). In addition, pendrin expression has been found in the kidney (33), mammary gland (31), uterus (39), testes (20), and placenta (2). No expression was found in fetal or adult brain, consistent with a peripheral cause of deafness (10,39).…”

Enhancement of sodium/iodide symporter expression in thyroid and breast cancer

“…A sulfate/iodide exchanger that is inhibited by 4,4 0 -diisothiocyanatostilbene 2,2 0 -disulfonic acid has been identified in rat mammary gland explants (Shennan 2001). Increased pendrin expression has also been reported in the lactating mammary gland (Rillema & Hill 2003). Since NIS is expressed on the basolateral membrane in the lactating mammary glands, other transporters, like pendrin, may mediate release of the trapped iodide into the lumen.…”

Renal Vacuolar H+-ATPase

“…Pendrin resides in the apical membrane of all nontype A intercalated cells (282,436,550) and is regulated by acid-base status (542), and genetic loss of pendrin function (PDS knock-out mice) leads to reduction of bicarbonate secretion in the isolated perfused cortical col- lecting ducts (436). Pendrin seems to have some sensitivity to DIDS (428,476). AE-4 is DIDS insensitive and is also expressed in non-type A intercalated cells; however, its subcellular localization seems to be species specific (i.e., apical in rabbit, basolateral in mouse and rat) and its physiological role is, therefore, uncertain (285,514).…”