Sex steroid metabolism in human peripheral blood mononuclear cells changes with aging

Context: Dehydroepiandrosterone ( DHEA) mainly exerts indirect action via downstream conversion toward sex steroids within peripheral target cells including immune cells. In vitro DHEA has been shown to enhance IL-2 release from T lymphocytes, whereas it inhibits IL-6 secretion. Conversely, aging is associated with a decline in both DHEA and IL-2, whereas IL-6 increases. Objective: The objective of the study was to investigate age- related differences in expression and functional activity of steroidogenic enzymes involved in downstream conversion of DHEA in peripheral blood mononuclear cells (PBMCs). Design: This study was cross- sectional. Participants/Setting: Healthy young men (n = 8; age range, 23 - 29 yr) and healthy middle- aged men ( n = 8; age range, 52 - 66 yr) were studied in an academic setting. Measures: mRNA expression of steroidogenic enzymes in PBMCs was measured by qualitative and quantitative RT- PCR analysis and enzyme activity assays after incubation of PBMCs with radiolabeled DHEA, 4- androstene- 3,17- dione ( androstenedione), and testosterone. Results: RT- PCR analysis showed expression of all enzymes required for DHEA conversion toward active androgens and to the immune-stimulatory metabolite androstenediol. Steroid conversion patterns indicated a particularly increased activity of 17 beta-hydroxysteroid dehydrogenase type 5 (17 beta-HSD5) in the older men, demonstrated by significantly higher conversion rates of DHEA to androstenediol and of androstenedione to testosterone ( all P <0.05). By contrast, conversion of DHEA to androstenedione via 3 beta-HSD occurred at a similar rate. Quantitative RT- PCR analysis revealed increased expression of 17 beta-HSD 5 mRNA in PBMCs from the older men. \ Conclusions: Our results provide evidence for significant changes in sex steroid metabolism by human PBMCs with aging, which may represent an endocrine link to immune senescence.