Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion

Meijing Wang, Yue Wang, Aaron Abarbanell, Jiangjing Tan, Brent Weil, Jeremy Herrmann, Daniel R. Meldrum

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)138-144
Number of pages7
JournalSurgery
Volume146
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Transducers
Reperfusion
Testosterone
Ischemia
Cytokines
Flutamide
Dihydrotestosterone
Castration
Down-Regulation
Androgen Receptors
Reperfusion Injury
Myocardium
Western Blotting

ASJC Scopus subject areas

  • Surgery

Cite this

Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion. / Wang, Meijing; Wang, Yue; Abarbanell, Aaron; Tan, Jiangjing; Weil, Brent; Herrmann, Jeremy; Meldrum, Daniel R.

In: Surgery, Vol. 146, No. 2, 08.2009, p. 138-144.

Research output: Contribution to journalArticle

Wang, Meijing ; Wang, Yue ; Abarbanell, Aaron ; Tan, Jiangjing ; Weil, Brent ; Herrmann, Jeremy ; Meldrum, Daniel R. / Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion. In: Surgery. 2009 ; Vol. 146, No. 2. pp. 138-144.
@article{939e67d6921b4ae79518569198b7aa3d,
title = "Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion",
abstract = "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.",
author = "Meijing Wang and Yue Wang and Aaron Abarbanell and Jiangjing Tan and Brent Weil and Jeremy Herrmann and Meldrum, {Daniel R.}",
year = "2009",
month = "8",
doi = "10.1016/j.surg.2009.03.035",
language = "English",
volume = "146",
pages = "138--144",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

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

UR - http://www.scopus.com/inward/citedby.url?scp=67650526442&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2009.03.035

DO - 10.1016/j.surg.2009.03.035

M3 - Article

VL - 146

SP - 138

EP - 144

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 2

ER -