RETINOIC ACID AND THYROID-HORMONE REGULATE PLACENTAL-LACTOGEN EXPRESSION IN HUMAN TROPHOBLAST CELLS

In this study, we have demonstrated that retinoic acid (RA) and thyroid hormone (T-3) stimulate the synthesis and release of human placental lactogen (hPL), one of the major secretory products of syncytiotrophoblast cells. Enzymatically, dispersed trophoblast cells from term placentas exposed continuously to RA (0.5 mu M) and T-3 (0.1 mu M) for 5 days released significantly more hPL than control cells after 3 days of exposure (P < 0.001 in each instance). On days 4 and 5, the amounts of hPL released by cells exposed to RA and T-3 were approximately 3- and 5-fold higher than those in control cells, respectively. The stimulation by both RA and T-3 was dose dependent and was accompanied by stimulation of hPL messenger RNA levels. RA and T-3 caused 3.5- and 5.6-fold increases, respectively, in chloramphenicol acetyltransferase activity in BeWo choriocarcinoma cells transfected transiently with a 2.3-kilobase (kb) fragment of the hPL promoter (-2300 to 2 basepairs) coupled to a chloramphenicol acetyltransferase reporter gene. Deletion construct analysis of the hPL promoter (2.3, 1.2, and 0.5 kb) indicated that the T-3- and RA-responsive elements are localized -0.5 to -1.2 kb up-stream from the transcriptional start site(+1), where several consensus RA- and T-3-responsive element sites are present. These results indicate that RA and T-3 stimulate the synthesis and release of hPL by a mechanism involving hPL gene transcription and further support a role for these steroids in placental function.