TRANSCRIPTIONAL ACTIVATION OF CYTOCHROME-P450 SIDE-CHAIN CLEAVAGE ENZYME EXPRESSION DURING TROPHOBLAST CELL-DIFFERENTIATION

The purpose of this study was to investigate P450scc expression during trophoblast differentiation. Biochemical characteristics of P450scc p rotein and mRNA identified in rat trophoblast tissues were similar to those identified in the rat adrenal gland. Furthermore, P450scc was lo calized to trophoblast giant cells. This observation prompted an exami nation of progesterone biosynthesis and P450scc expression in Rcho-1 c ells. Rcho-1 cells were derived from a transplantable rat choriocarcin oma, their differentiation can be regulated, and they have the capacit y to express the trophoblast giant cell phenotype. Progesterone was pr oduced by Rcho-1 cells and increased approximately 100-fold as the cel ls progressed from proliferation to differentiation. P450scc protein a nd mRNA accumulation also increased during trophoblast differentiation . P450scc expression within the Rcho-1 cell line was restricted to tro phoblast giant cells. To further investigate the regulation of P450scc expression during trophoblast differentiation, we examined a plasmid construct, containing 894 base pairs of DNA 5' upstream from the P450s cc transcriptional start site linked to a human growth hormone reporte r gene, following stable transfection into Rcho-1 cells. The transfect ed P450scc regulatory DNA permitted the expression of human growth hor mone which paralleled expression of the endogenous P450scc gene, In co nclusion, transcriptional activation of the P450scc gene accompanies t rophoblast giant cell differentiation.