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Sex Steroid Metabolism in Human Peripheral Blood Mononuclear Cells Changes with Aging

Department of Medicine, Endocrine and Diabetes Unit (F.H., D.G.D., B.A.), University of Würzburg, 97080 Würzburg, Germany; and Division of Medical Sciences (F.H., S.B.S., M.Q., P.M.S., W.A.), Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Address all correspondence and requests for reprints to: Dr. Wiebke Arlt, M.D., Division of Medical Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom. E-mail: w.arlt{at}bham.ac.uk.

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 17ß-hydroxysteroid dehydrogenase type 5 (17ß-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 3ß-HSD occurred at a similar rate. Quantitative RT-PCR analysis revealed increased expression of 17ß-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.

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