Dual reporter systems in yeast and mammalian cells for assessing progesterone receptor modulators

In the present study we describe the set-up of a new one-hybrid reporter gene assay in Saccharomyces cerevisiae composed of the human progesterone receptor fused to the DNA-binding domain of the yeast transcriptional activator Gal4. This assay allows the convenient estimation of receptor mediated progestogenic as well as antiprogestogenic actions of compounds. The induction of the beta-galactosidase reporter gene expression correlated well with the progesterone receptor affinity and the concentration of the progestins tested. The results corresponded to those obtained from a reporter gene assay in the cancer cell line CV-1 and in vitro binding experiments using rabbit uterus cytosol. In both the yeast and CV-1 cells the activity of antiprogestins was detectable by inhibition of the progestin-induced reporter gene expression. Secondary reporter genes under the transcriptional control of receptor unrelated promoters have been introduced into yeast and mammalian test strains to distinguish between specific receptor mediated antihormone actions and nonspecific effects on cellular metabolism.