Calcium influx pathways during mammary gland development and lactation

The mammary gland is an organ that is extensively remodeled during critical stages in development such as pregnancy, lactation and involution with concomitant temporal changes in gene expression. During the mammary gland’s redevelopment the processes of proliferation and apoptosis are fundamental. The calcium ion is critical for the control of both these processes and is essential for secretion into milk during lactation. The pathways for calcium efflux into milk from the cell are not well understood but are likely to involve secretory vesicles and the active calcium transporter, plasma membrane calcium ATPase (PMCA). The PMCA isoform PMCA2bw is upregulated over 100 fold in the rat mammary gland during lactation and is proposed to reside on the apical membrane and thus have a role in calcium secretion into milk. In contrast little is known about the mechanism of calcium influx across the basolateral membrane during lactation, although a role for the extracellular calcium sensing receptor (CaR) in regulating this process has been proposed. In these studies using mammary gland isolated from null-parous, pregnant, lactating and involuting mice we examined the presence of CaR and the temporal changes in the expression of two calcium influx channels with reported links to CaR, transient receptor potential (TRP) C1 and C6. Using real time RT-PCR we were unable to detect the CaR in a mammary gland from a lactating mouse, despite amplification from a mouse kidney control. TRPC1 and TRPC6 declined during pregnancy with further down regulation during lactation and involution. Our study suggests that TRPC1 and TRPC6 are not the channels involved in basolateral calcium influx during lactation and questions the involvement of CaR in this process as wel