title: Estrogen inhibits hyperthermia-induced expression of heat-shock protein 72 and cardioprotection against ischemia/reperfusion injury in female rat heart.
abstract: There is still controversy as to whether estrogen inhibits or enhances heat-shock protein (HSP72) expression in the heart. To evaluate the gender difference, whole-body hyperthermia (HT, 43 degrees C for 20 min) or normothermia (NT, 37 degrees C for 20 min) was applied to both male and female rats. Twenty-four hours after each thermo-treatment, the heart was isolated for either Western blot analysis or isolated-perfused heart experiments. Induction of HSP72 expression and post-ischemic recovery of left ventricular (LV) function was pronounced in male than in female heart. To evaluate the effect of estrogen, female rats received ovariectomy. One week after the operation, ovariectomized rats were treated with 17beta-estradiol in a single administration of 4, 40, or 400 mug/kg or vehicle (placebo) intraperitoneally (IP), followed by HT or NT at 6 h after the administration. In the placebo-treated ovariectomized female, HT-induced cardiac HSP72 expression was more remarkable with better LV functional recovery than sham-operated gonadally intact female. Treatment with 17beta-estradiol reduced HT-induced cardiac HSP72 overexpression and abolished better LV functional recovery observed in placebo-treated ovariectomized female. Inhibition of HT-induced HSP72 expression was in association with the inhibition of activation of heat-shock factor 1 (HSF1). In cultured rat neonatal cardiomyocytes, prior exposure to H(2)O(2)-induced HSP72 expression and rendered protection against hypoxia/reoxygenation, which was attenuated by the treatment with 17beta-estradiol. The washout of 17beta-estradiol for 48 h recovered the H(2)O(2)-induced HSP72 expression and tolerance against hypoxia/reoxygenation. Our results suggest that the male heart is more sensitive than gonadally intact female heart in terms of response to HT to express HSP72 in association with protection against ischemic insult. This observation may be due to the inhibitory effects of estrogen on HSP72 expression at a transcriptional level.
authors.affiliation: Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Ooie
authors.forename: Masashi
authors.initials: M
authors.lastname: Ichinose
authors.forename: Masahide
authors.initials: M
authors.lastname: Hara
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yonemochi
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Saikawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D000818:Animals; D018834:Chaperonin 60 / Q000032:analysis / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D018869:Heat-Shock Response / Q000187:drug effects*; D006979:Hyperthermia, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014157:Transcription Factors
chemical_list: D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D014157:Transcription Factors; D004958:Estradiol