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


METHODS
This study was cross-sectional.


METHODS
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.


METHODS
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 17beta-hydroxysteroid dehydrogenase type 5 (17beta-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 3beta-HSD occurred at a similar rate. Quantitative RT-PCR analysis revealed increased expression of 17beta-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.
Hammer
Fabian
F
Department of Medicine, Endocrine and Diabetes Unit, University of Würzburg, 97080 Würzburg, Germany.
Drescher
Daniel G
DG
Schneider
Susanne B
SB
Quinkler
Marcus
M
Stewart
Paul M
PM
Allolio
Bruno
B
Arlt
Wiebke
W
D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D042944:Cholestenone 5 alpha-Reductase / Q000032:analysis; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013739:Testosterone; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases; D042944:Cholestenone 5 alpha-Reductase