Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?
Bottom Line: These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL.Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration.Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor.
Affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. email@example.comShow MeSH
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Mentions: Upon activation of the prolactin receptor, the JAK-STAT signalling pathway is activated, with STAT5 as the primary mediator of prolactin action . Additionally, ERK1/2 phosphorylation is also a major downstream target of prolactin receptor signalling . Hence, we investigated the phosphorylation of STAT5 and ERK1/2 after exposure of 2H11 cells to a dose range of prolactin. As shown in Figure 1, prolactin induced a concentration-dependent phosphorylation of ERK1/2, starting at 10 μg/l and culminating at 1000 μg/l (lane 5–8). Phosphorylation of ERK1/2 was decreased when using 10,000 μg/l prolactin (lane 9). Prolactin also induced the phosphorylation of STAT5, starting at 10 μg/l and peaking at 10,000 μg/l (lane 5–9). Moreover, ERK1/2 and STAT5 phosphorylation induced by prolactin was completely abolished by addition of 20-fold molar excess of the prolactin receptor antagonist del1-9-G129R-hPRL (lane 1 and 2 compared to 6 and 7). The antagonist alone, even at extremely high concentrations (10,000 μg/l), failed to notably induce signalling (lane 3 and 4) (Fig. 1). Overall, these data demonstrate that prolactin has a direct effect on endothelial cells, which is mediated by the prolactin receptor.
Affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. firstname.lastname@example.org