Orchiectomy reduces susceptibility to renal ischemic injury: a role for heat shock proteins

Biochem Biophys Res Commun. 2005 Mar 4;328(1):312-7. doi: 10.1016/j.bbrc.2004.12.177.


In previous studies we demonstrated that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney ischemia/reperfusion (I/R) injury. Although molecular chaperones such as heat shock proteins (HSPs) have been implicated as protective agents in the pathophysiology of I/R injury, their roles in gender differences in susceptibility to renal I/R injury remain to be defined. Here we demonstrate that orchiectomy increases the basal and post-ischemic expression of HSP-27 in kidney tubular epithelial cells, but not HSP-72, glucose-regulated protein (GRP)-78 or GRP-94 expression. Orchiectomy prevents the disruption of the actin cytoskeleton and renal functional disorders induced by I/R, when compared with intact male mice or orchiectomized mice treated with dihydrotestosterone, a non-aromatizable isoform of testosterone. Thus, the protection afforded by orchiectomy is associated with increased expression of HSP-27, a heat shock protein important for maintenance of actin cytoskeletal integrity. These findings indicate that testosterone inhibits the heat shock response and may provide a new paradigm for design of therapies for I/R injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Actins / ultrastructure
  • Animals
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Dihydrotestosterone / pharmacology
  • Disease Susceptibility / metabolism
  • Disease Susceptibility / surgery
  • Heat-Shock Proteins / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Diseases / surgery*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orchiectomy*
  • Reperfusion Injury / complications
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / surgery*
  • Testosterone / metabolism*


  • Actins
  • Heat-Shock Proteins
  • Dihydrotestosterone
  • Testosterone