Аннотация:Progesterone (P4) plays an important role in female reproductive functions. It is involved in regulation of proliferation and apoptosis as well. P4 action is mediated by two types of receptors - nuclear receptors (nPRs) and membrane receptors (mPRs). The effects of P4 mediated by different types of receptors can vary considerably. In our laboratory, two mPRs selective ligands were identified: 19-hydroxypregn-4-en-20-one (I) and 19-hydroxy-5β-pregn-3-en-20-one (II). The purpose of this work is to study the mechanisms of action of P4 and mPRs selective ligands on the expression of genes associated with apoptosis in pancreatic adenocarcinoma BxPC3 cells. These cells have high level of mPRs mRNA and lack of nPRs mRNA. First of all we tested the effect of different concentrations of P4 and its analogues on transcription of the genes coding for apoptosis-related factors in BxPC3 cells. Secondly we use specific protein kinase inhibitors to determine the involvement of p38 MAPK and JNK in hormone-dependent changes on expression of apoptosis-associated genes. All three compounds did not affect the expression of Apaf1, bcl-2-alpha, BIK, Casp8, FAS and TP53 genes. In the absence of inhibitors, only compound II significantly increased the expression of proapoptotic DAPK and HRK genes at the maximal concentration used. In the presence of the p38 MAPK inhibitor, the compound II did not influence DAPK expression, but the expression of the HRK gene was still increased. The JNK inhibitor did not change the effects of compound II on DAPK and HRK genes expression. At the same time, P4 and compound I also increased the level of HRK mRNA at the maximal concentration used. Thus, compound II enhances the expression of two pro-apoptotic factors out of nine studied, and these changes are not dependent on JNK pathway. The effect of compound II on the level of DAPK mRNA is mediated by p38 MAPK. The work was supported by Russian Foundation for Basic Research (project 17-04-00234).