This study was undertaken to determine whether transforming growth factor a (TGF-a) regulates the production of mouse placental lactogen I (mPL-I) and mPL-II in a manner that is similar to that of epidermal growth factor (EGF), which was previously shown to stimulate mPL-I secretion and inhibit mPL-II secretion. In contrast to the activity of EGF, human (h) and rat (r) TGF-a (each at 100 ng/ml) inhibited secretion ofmPL-I by placental cells isolated from mice on day 7 of pregnancy. Maximum inhibition of mPL-I secretion occurred on the third day of a 5-day culture period and ranged between 37% and 56% in multiple trials. Incubation of cells with hTGF-a and EGF was not followed by a change in the mPL-I concentration of the medium, suggesting the peptides antagonized each other's effects. hTGF-a and rTGF-a inhibited secretion of mPL-II; maximum inhibition ranged between 62% and 84% in multiple trials. The lowest concentrations of hTGF-a that affected mPL-I and mPL-II secretion were 10 ng/ml and 1 ng/ml, respectively. EGF and hTGF-a bound to the same receptors on placental cells, as assessed by cross-linking, and both peptides stimulated receptor phosphorylation, as assessed by Western blot analysis.There are three types of mPL-containing cells in placental cultures: cells that contain only mPL-I, cells that contain only mPL-II, and cells that contain both mPLs. The percentage of each type of mPL-containing cell in the culture was determined by immunostaining. hTGF-ca affected the differentiation of the subpopulations of PL-containing cells in a manner that differed from that of EGF. The data suggest that TGF-a and EGF do not regulate the production of mPL-I and mPL-II in a similar manner.Transforming growth factor a (TGF-a) and epidermal growth factor (EGF) share 30-40% amino acid sequence homology and are believed to act by binding to a common receptor designated the EGF receptor (1, 2). As expected from their binding to a common receptor, effects of EGF and TGF-a have generally been similar, although qualitative and quantitative differences in the responses induced by the peptides have been observed (3-10). We recently examined effects of EGF on the secretion of mouse placental lactogen I (mPL-I) and mPL-II (11), which are prolactin-like hormones produced by trophoblast giant cells (12). mPL-I is present at high concentration in maternal blood on days 9 and 10 of pregnancy (13). mPL-II appears in maternal blood on day 9 of pregnancy and is present at relatively high concentration during the last week of pregnancy (term = 19 days) (14). EGF stimulated the secretion of mPL-I by mouse placental cells from days 7 and 9 of pregnancy and inhibited secretion of mPL-II by cells from days 7, 9, and 12. In addition, the sensitivity of mPL-II-producing cells to EGF declined between days 7 and 12 of pregnancy. These data suggested that EGF may play a role in the shift in placental PL production from mPL-I to mPL-II that occurs at midpregnancy. Effects of TGF-a in this system were not examined. Since TGF-a mRNA and/or...