Mammary gland differentiation inversely correlates with GDF-8 expression

GDF-8 is recognised as an inhibitor of muscle cell growth and differentiation. Although initially thought to be restricted to muscle cells it is now accepted that GDF-8 expression has a broader tissue distribution. We demonstrate GDF-8 expression in the mouse mammary gland, which is predominantly associated with epithelial cells and displays an inverse correlation to the differentiated state of the gland. Specifically, the highest GDF-8 mRNA levels correlate with periods of maximal ductal growth, diminish as pregnancy progressed and are down-regulated to minimal levels by the onset of lactation as the epithelium differentiates. A similar profile is observed for both GDF-8 protein processing and reflects Smad2/3 phosphorylation profile. However, in contrast to muscle cells, GDF-8 neither reduces proliferation nor induces p21 expression levels in mammary epithelial cells. These data implicate a role for GDF-8 in mammary epithelial cell differentiation and demonstrate that GDF-8 has cell-type specific activities.