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Androgen Effects On Soluble Epoxide Hydrolase Expression and Cardioprotection
Author(s) -
Batchu Sri Nagarjun,
Pawa Jasmine,
Zhang Yunfang,
Myers Page,
Clark James,
MillerDegraff Laura,
Zeldin Darryl C,
Sinal Christopher J,
Goralski Kerry,
Seubert John M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.479.45
Subject(s) - epoxide hydrolase 2 , medicine , endocrinology , chemistry , androgen , ischemia , testosterone (patch) , enzyme , biochemistry , hormone
Androgens can regulate hepatic and renal expression of soluble epoxide hydrolase (sEH or EPHX2) which metabolize epoxyeicosatrienoic acids (EETs) to less bioactive metabolites. To examine the role of EETs and testosterone in ischemia reperfusion injury, mice with targeted disruption of soluble epoxide hydrolase (sEH null) were utilized. Gonadectomies were performed on randomly selected mice either at post‐natal day1 (PN1) or 3 months of age (cast). Hearts were excised and perfused in a Langendorff apparatus, subjected to 20min of ischemia followed by 40min of reperfusion. PCR analysis of EPHX2, αMHC, βMHC and GAPDH expression was performed. Improved postischemic recovery of left ventricular function was observed in male sEH null mice compared to WT (LVDP: 63±3 and 22±2%), which was diminished in females (LVDP: 40±6 and 22±5%). Gonadectomy improved postischemic recovery of LVDP (WT: control 25±3; PN1 68±11; cast 67±12%; sEH null: control 64±3; cast 88±14%). Renal expression of EPHX2 decreased following gonadectomy and was restored following androgen treatment. In contrast, no differences in cardiac EPHX2 expression were observed between treatment groups. Increased βMHC:αMHC ratio gene expression in gonadectomized mice was observed. While gender differences play a role in postischemic functional recovery our data would suggest that androgens do not influence cardiac expression of sEH.