Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart.
The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels.
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Furong
F
Zhang
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Xuming
X
Yu
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Chunyan
C
He
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Xiufang
X
Ouyang
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Jinhua
J
Wu
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Jie
J
Li
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Junjie
J
Zhang
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Xuejiao
X
Duan
Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Yu
Y
Wan
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: yuejiang@whu.edu.cn.
Jiang
J
Yue
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics
D001095:Arachidonic Acids; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D019883:Alkyl and Aryl Transferases
Arachidonic acid; Cytochrome P450; Growth hormone; Sexual dimorphism