Effect of insulin on iodide uptake in mouse mammary gland explants.

Studies were carried out primarily to assess the role of insulin in regulating iodide uptake in the mammary gland. Using cultured mammary gland explants from virgin and pregnant mice (12-14 days into gestation), insulin (1 microg/ml) was shown to stimulate iodide uptake after a 2-day exposure period. The effect of insulin was manifested by itself, as well as in the presence of cortisol and prolactin. Optimal iodide uptake was observed when tissues were treated with all three lactogenic hormones (insulin, cortisol, and prolactin). In a time-course experiment, the effect of insulin alone was initially observed after a 10-hr treatment; the effect was maintained for 30 hr. In dose-response studies, 1 ng/ml insulin elicited a significant effect after 24 hr in culture; a maximal effect was achieved with 50-100 ng/ml insulin. The optimal cortisol concentration for a maximum stimulation of iodide uptake was 10(-7)M. In a quantitative Western blot analysis employing an antibody to the sodium-iodide symporter, insulin stimulated an upregulation of the transporter protein after a 4-, 8-, or 20-hr treatment with insulin. Perchlorate and thiocyanate abolished the insulin effect on iodide uptake, further suggesting that the insulin response occurs via a stimulation of the sodium-iodide symporter. Clearly, insulin is an important and essential hormone in the lactogenic hormone complex for regulating iodide uptake in the mammary gland, but maximal expression of iodide uptake is only expressed when all three lactogenic hormones are present.