ИСТИНА

Many synthetic progestins possess proliferative as well as antiproliferative activity in vivo, depending on the presence and ratio between different types of the nuclear and membrane receptors in the various tissues. There is a need to explore progestins’ transcriptive activity in simple systems to identify selective ligands for different receptor isoforms. We made an attempt to estimate newly synthesized group of 14 pregna-D-pentaranes and 4 3-O-methoxyimino derivatives of progesterone with known binding characteristics upon their capacity to influence transcription activity (TA) of the human nuclear progesterone receptor (nPR-B) in vitro, enabling to except effects of these steroids mediated through all the rest receptors besides nPR-B. Yeast were transformed with plasmid containing nPR-B gene and LacZ reporter gene, allowing to assay TA. Reliability of method was verified with a native agonist progesterone and synthetic antagonist – mifepristone. 16-alpha-17-alpha-cyclohexanoprogesterone (CHP) and 16-alpha-17-alpha cyclopropanoprogesterone (CPP) were detected as full progesterone agonists upon the relative transcription activity (RTA) with significantly lower EC50 for CHP. These data support the previous findings of lower agonistic activity of CPP in Clauberg-Mcfail and Corner-Allen tests on rabbits’ uterus due to prevalence of the nPR-A in this tissue. It was assumed that CHP may act as a strong discriminated nPR-B agonist with great potential in treating the ovarian and endometrial cancers.