Aging and luteinizing hormone effects on reactive oxygen species production and DNA damage in rat leydig cells

Matthew C. Beattie, Haolin Chen, Jinjiang Fan, Vassilios Papadopoulos, Paul Miller, Barry R. Zirkin

Research output: Contribution to journalArticlepeer-review

Abstract

We observed previously that after long-term suppression of luteinizing hormone (LH) and thus of Leydig cell steroidogenesis, restimulation of the Leydig cells by LH resulted in significantly higher testosterone production than by age-matched cells from control rats. These studies suggest that stimulation over time may elicit harmful effects on the steroidogenic machinery, perhaps through alteration of the intracellular oxidant-toantioxidant balance. Herein we compared the effects of LH stimulation on stress response genes, formation of intracellular reactive oxygen species (ROS), and ROS-induced damage to ROS-susceptible macromolecules (DNA) in young and in aged cells. Microarray analysis indicated that LH stimulation resulted in significant increases in expression of genes associated with stress response and antiapoptotic pathways. Short-term LH treatment of primary Leydig cells isolated from young rats resulted in transiently increased ROS levels compared to controls. Aged Leydig cells also showed increased ROS soon after LH stimulation. However, in contrast to the young cells, ROS production peaked later and the time to recovery was increased. In both young and aged cells, treatment with LH resulted in increased levels of DNA damage but significantly more so in the aged cells. DNA damage levels in response to LH and the levels of intracellular ROS were highly correlated. Taken together, these results indicate that LH stimulation causes increased ROS production by young and aged Leydig cells and that while DNA damage occurs in cells of both ages, there is greater damage in the aged cells.

Original languageEnglish (US)
Article number100
JournalBiology of reproduction
Volume88
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Aging
  • DNA damage
  • DNA repair
  • Leydig cell
  • ROS

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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