Cyclic Adenosine 3′,5′-Monophosphate Stimulation of Placental Proliferin and Proliferin-Related Protein Secretion

To identify factors that regulate proliferin (PLF) and PLF-related protein (PRP) secretion by the mouse placenta, placental cells from day 9 of pregnancy were cultured for up to 5 days, and PLF and PRP release into the medium was assessed by RIA. Transforming growth factor-α, interleukin-1α, and interleukin-6 did not regulate either PLF or PRP secretion. However, treatment of primary placental cell cultures with 8-bromo-cAMP, cholera toxin, or forskolin resulted in 2-to 3-fold increases in the percentages of PLF- and PRP-producing cells in the population and corresponding increases in both PLF and PRP messenger RNA and secreted protein. The increase in the number of PLF-producing cells was accompanied by an increase in the number of cells expressing both PLF and mouse placental lactogen-I. These data suggest that cAMP levels can regulate trophoblast giant cell differentiation and, consequently, the amount of PLF and PRP secretion.