Prolactin stimulation of iodide uptake and incorporation into protein is polyamine-dependent in mouse mammary gland explants

Previous studies have demonstrated that the prolactin stimulation of most l actational processes (casein, lactose, and triglyceride synthesis) requires an earlier stimulating effect of prolactin on the synthesis of the polyami nes, Spermidine appears to be the specific polyamine required for prolactin to enhance milk product synthesis. Inorganic iodide is present in milk at more than an order of magnitude higher concentration than that of the mater nal plasma. Since prolactin stimulates iodide accumulation in milk, the goa l of these studies was to determine the role of the polyamines in this horm one response. Two drugs were employed in these studies: DFMO (difluoromethy lornithine), which inhibits ornithine decarboxylase, and MGBG [methylglyoxa l bis(guanyl-hydrazone)], which inhibits S-adenosyl methionine decarboxylas e. In mammary gland explants from midpregnant (10-14 days of pregnancy) mic e, MGBG at 100 mu M abolished the prolactin stimulation of iodide uptake an d incorporation into milk proteins, whereas DFMO caused a concentration-dep endent inhibition of the PRL response. Selected sensitivity of the MGBG and DFMO inhibitions was validated by a reversal of the drug inhibitions with the addition of 1 mM spermidine to the culture medium. These data suggest t hat the polyamine signaling pathway is involved in the prolactin stimulatio n of iodide uptake into milk.