TY - JOUR
T1 - Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion
AU - Wang, Meijing
AU - Wang, Yue
AU - Abarbanell, Aaron
AU - Tan, Jiangjing
AU - Weil, Brent
AU - Herrmann, Jeremy
AU - Meldrum, Daniel R.
PY - 2009/8
Y1 - 2009/8
N2 - Background: Signal transducer and activator of transduction 3 (STAT3) pathway has been shown to be cardioprotective. We observed decreased STAT3/suppressor of cytokine signaling 3 (SOCS3) in male hearts, which was associated with worse postischemic myocardial function compared with females. However, it is unclear whether this downregulation of myocardial STAT3/SOCS3 is due to testosterone in males. We hypothesized that after ischemia/reperfusion (I/R), (1) endogenous testosterone decreases myocardial STAT3 and SOCS3 in males, and (2) administration of exogenous testosterone reduces myocardial STAT3/SOCS3 in female and castrated male hearts. Methods: To study this, hearts from I/R injury (Langendorff) were homogenized and assessed for phosphorylated-STAT3 (p-STAT3), total-STAT3 (T-STAT3), SOCS3, and GAPDH by Western blot. We grouped age-matched adult males, females, castrated males, males with androgen receptor blocker-flutamide implantation, females, and castrated males with chronic (3-week) 5α-dihydrotestosterone (DHT) release pellet implantation or acute (5-minute) testosterone infusion (ATI) before ischemia (n = 5-9 per group). Results: Castration or flutamide treatment significantly increased SOCS3 expression in male hearts after I/R. However, only castration increased myocardial STAT3 activation. Notably, DHT replacement or ATI decreased markedly myocardial STAT3/SOCS3 in castrated males and females subjected to I/R. Conclusion: These results suggest that endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after I/R. This represents the initial demonstration of testosterone-downregulated STAT3/SOCS3 signaling in myocardium.
AB - Background: Signal transducer and activator of transduction 3 (STAT3) pathway has been shown to be cardioprotective. We observed decreased STAT3/suppressor of cytokine signaling 3 (SOCS3) in male hearts, which was associated with worse postischemic myocardial function compared with females. However, it is unclear whether this downregulation of myocardial STAT3/SOCS3 is due to testosterone in males. We hypothesized that after ischemia/reperfusion (I/R), (1) endogenous testosterone decreases myocardial STAT3 and SOCS3 in males, and (2) administration of exogenous testosterone reduces myocardial STAT3/SOCS3 in female and castrated male hearts. Methods: To study this, hearts from I/R injury (Langendorff) were homogenized and assessed for phosphorylated-STAT3 (p-STAT3), total-STAT3 (T-STAT3), SOCS3, and GAPDH by Western blot. We grouped age-matched adult males, females, castrated males, males with androgen receptor blocker-flutamide implantation, females, and castrated males with chronic (3-week) 5α-dihydrotestosterone (DHT) release pellet implantation or acute (5-minute) testosterone infusion (ATI) before ischemia (n = 5-9 per group). Results: Castration or flutamide treatment significantly increased SOCS3 expression in male hearts after I/R. However, only castration increased myocardial STAT3 activation. Notably, DHT replacement or ATI decreased markedly myocardial STAT3/SOCS3 in castrated males and females subjected to I/R. Conclusion: These results suggest that endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after I/R. This represents the initial demonstration of testosterone-downregulated STAT3/SOCS3 signaling in myocardium.
UR - http://www.scopus.com/inward/record.url?scp=67650526442&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2009.03.035
DO - 10.1016/j.surg.2009.03.035
M3 - Article
C2 - 19628067
AN - SCOPUS:67650526442
SN - 0039-6060
VL - 146
SP - 138
EP - 144
JO - Surgery
JF - Surgery
IS - 2
ER -