title: Sex steroid metabolism in human peripheral blood mononuclear cells changes with aging.
abstract: 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.
authors.affiliation: Department of Medicine, Endocrine and Diabetes Unit, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Hammer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Drescher
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Schneider
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
mesh_terms: 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
chemical_list: D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013739:Testosterone; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases; D042944:Cholestenone 5 alpha-Reductase