Milk lipids, important for infant growth and development, are produced and secreted by mammary gland under the regulation of steroid hormones, growth factors, and microRNAs (miRNAs). miR-221 has been identified in milk and adipocytes and it plays important roles in regulating normal mammary epithelial hierarchy and breast cancer stem cells; however, its roles in lipid metabolism in mammary epithelial cells (MECs), the cells of lipid synthesis and secretion, are as yet unknown. Through overexpression or inhibition of miR-221 expression, we found that it regulated lipid metabolism in MECs and was expressed differentially at various stages during murine mammary gland development. Inhibition of miR-221 expression increased lipid content in MECs through elevation of the lipid synthesis enzyme FASN, while overexpression of miR-221 reduced MEC lipid content. Moreover, the steroid hormones estradiol and progesterone decreased miR-221 expression with a subsequent increase in lipid formation in MECs. The expression of miR-221 was lower during lactation, which suggests that it may be involved in milk production. Therefore, miR-221 might be a useful target for influencing milk lipid production.
Keywords: Estradiol; Lactation; Lipid; Metabolism; MiR-221; Progesterone.
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