The role of nitric oxide in the biological activity of prolactin in the mouse mammary gland

In mouse mammary epithelial cells, prolactin transiently elevates nitric oxide (NO) to a maximum of 6 nmol/mg protein at 15 min, after which levels fall rapidly. This stimulation can be achieved by as little as 100 ng prolactin/ml and can be mimicked by 100 mug sodium nitroprusside/ml. NO is both necessary and sufficient to mediate the prolactin-induced redistribution of its receptor from internal pools to the cell surface. NO can also enhance DNA synthesis stimulated by submaximal prolactin concentrations (50 ng/ml), but it is not necessary at pharmacological prolactin concentrations (1 mug/ml). In contrast, NO completely inhibits alpha -lactalbumin production. In summary, prolactin transiently elevates NO to enhance DNA synthesis and suppress premature differentiation; thereafter, NO declines, DNA synthesis ceases and differentiation proceeds. This data suggest that NO may mediate some of the effects of prolactin on growth in the mammary gland. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.