Transcriptional activation of cytochrome P450 side chain cleavage enzyme expression during trophoblast cell...

The purpose of this study was to investigate P450scc expression during trophoblast differentiation. Biochemical characteristics of P450scc protein and mRNA identified in rat trophoblast tissues were similar to those identified in the rat adrenal gland. Furthermore, P450scc was localized to trophoblast giant cells. This observation prompted an examination of progesterone biosynthesis and P450scc expression in Rcho-1 cells. Rcho-1 cells were derived from a transplantable rat choriocarcinoma, their differentiation can be regulated, and they have the capacity to express the trophoblast giant cell phenotype. Progesterone was produced by Rcho-1 cells and increased approximately 100-fold as the cells progressed from proliferation to differentiation. P450scc protein and mRNA accumulation also increased during trophoblast differentiation. P450scc expression within the Rcho-1 cell line was restricted to trophoblast 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 P450scc transcriptional start site linked to a human growth hormone reporter gene, following stable transfection into Rcho-1 cells. The transfected P450scc regulatory DNA permitted the expression of human growth hormone which paralleled expression of the endogenous P450scc gene. In conclusion, transcriptional activation of the P450scc gene accompanies trophoblast giant cell differentiation.