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 interleukin-2 (IL-2) release from T lymphocytes while it inhibits IL-6 secretion. Vice versa, aging is associated with a decline in both DHEA and IL-2 while IL-6 increases.

Objective. 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. Cross-sectional study.

Participants/Setting. Healthy young men (n = 8; age range 23-29 yr) and healthy middle-aged men (n = 8; age range 52-66 yr) studied in an academic setting.

Measures. mRNA expression of steroidogenic enzymes in PBMCs by qualitative and quantitative RT-PCR analysis and enzyme activity assays following incubation of PBMCs with radiolabeled DHEA, 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-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-HSD occurred at a similar rate. Quantitative RT-PCR analysis revealed increased expression of 17-HSD5 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.