Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells

Kristen L. Osterlund, Robert J. Handa, Rayna J. Gonzales

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1β. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1β, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and-independent mechanisms, depending on the physiological state of the cell.

Original languageEnglish (US)
Pages (from-to)E838-E845
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume298
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Androgen
  • Inflammation
  • Interleukin-1β
  • Lipopolysaccharide
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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