Epigenetic regulation of steroidogenic enzymes expressed in peripheral blood mononuclear cells from healthy individuals and from patients with chronic lymphocytic leukemia

Abstract

Sex hormone synthesis occurs in various organs and tissues besides the gonads, such as adrenal glands, brain, intestines, skin, fat, bone, and cells of the immune system. Regarding the latter, it is still not clear which pathways are active, and if they are modified in case of illness of the immune system. Our goal in this study was to determine mRNA expression of different steroidogenic enzymes in peripheral blood mononuclear cells (PBMCs) from healthy individuals of both sexes and of different ages, and then to compare their expression between healthy individuals and patients with Chronic Lymphocytic Leukemia (CLL). Furthermore, to elucidate possible mechanisms that regulate enzyme expression, we analyzed epigenetic events like promoter methylation. We determined that normal cells of the immune system, regardless of sex and age, expressed P450 side chain cleavage (P450scc), cytochrome P450 17α-hydroxylase/c17,20-lyase (P45017α), 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), steroid 5 α reductase (5α-R) types 1, 2 and 3, 3α-hydroxysteroid dehydrogenase (3α-HSD) type 3, and 17β-hydroxysteroid dehydrogenase (17β-HSD) types 1, 3 and 5. We also established that 5α-R 1, 5α-R 3, 3α-HSD 3, 17β-HSD 1 and 17β-HSD 5 expression was altered in CLL patients, and that promoter regions of 5α-R 1, 17β-HSD 1 and 17β-HSD 5 were diferentially methylated. These results suggest that steroidogenic pathways may be affected in CLL cells, and this could be related to disease pathogenesis.