Transforming growth factor-alpha regulates subpopulation of giant cells which secrete mouse placental lactogen-I (mPL-I) and/or mPL-II at midpregnancy.

The aim of this study was to determine whether transforming growth factor-alpha (TGF-alpha) regulates expression of mouse placental lactogen-I (mPL-I) and mPL-II at midpregnancy in vitro. Treatment of placental cells from day 9 of pregnancy with TGF-alpha resulted in stimulation of mPL-I secretion and inhibition of mPL-II secretion in a time- and dose-dependent manner without changing the amount of newly synthesized trichloroacetic acid precipitable proteins and cell viability. Moreover, TGF-alpha increased the intra-cellular mPL-I concentration and immuno-precipitable newly synthesized mPL-I concentration both in the medium and cells. TGF-alpha increased the number of cells containing only mPL-I and cells containing both mPL-I and mPL-II, but decreased that of the cells containing only mPL-II assessed by double immunocytochemistry. TGF-alpha increased the number of cells releasing only mPL-I but decreased the number of cells releasing only mPL-II, however TGF-alpha did not affect the number of cells releasing both mPL-I and mPL-II assessed by sequential reverse hemolytic plaque assay (RHPA). TGF-alpha decreased the expression of mPL-II mRNA, but did not change the expression of mPL-I mRNA. In situ hybridization for epidermal growth factor receptor (EGF-R) after RHPA for mPL-I indicated that giant cells releasing mPL-I express EGF-R mRNA. These findings suggest that TGF-alpha regulates the subpopulation of giant cells which produces and releases mPL-I and mPL-II and it results in an increase of mPL-I secretion and decrease of mPL-II secretion, and suggests possible post-transcriptional stimulation of mPL-I secretion and transcriptional inhibition of mPL-II secretion by TGF-alpha. Giant cells releasing mPL-I express EGF-R mRNA, suggesting direct regulation of giant cell differentiation by EGF and TGF-alpha at midpregnancy.