title: Sex and sex hormones in cardiac stress--mechanistic insights.
abstract: Important sex differences in the onset and characteristics of cardiovascular disease are evident, yet the mechanistic details remain unresolved. Men are more susceptible to cardiovascular disease earlier in life, though younger women who have a cardiovascular event are more likely to experience adverse outcomes. Emerging evidence is prompting a re-examination of the conventional view that estrogen is protective and testosterone a liability. The heart expresses both androgen and estrogen receptors and is functionally responsive to circulating sex steroids. New evidence of cardiac aromatase expression indicates local estrogen production may also exert autocrine/paracrine actions in the heart. Cardiomyocyte contractility studies suggest testosterone and estrogen have contrasting inotropic actions, and modulate Ca(2+) handling and transient characteristics. Experimentally, sex differences are also evident in cardiac stress responses. Female hearts are generally less susceptible to acute ischemic damage and associated arrhythmias, and generally are more resistant to stress-induced hypertrophy and heart failure, attributed to the cardioprotective actions of estrogen. However, more recent data show that testosterone can also improve acute post-ischemic outcomes and facilitate myocardial function and survival in chronic post-infarction. The myocardial actions of sex steroids are complex and context dependent. A greater mechanistic understanding of the specific actions of systemic/local sex steroids in different cardiovascular disease states has potential to lead to the development of cardiac therapies targeted specifically for men and women.
authors.affiliation: Department of Physiology, University of Melbourne, Victoria, Australia. Electronic address: belljr@unimelb.edu.au.
authors.forename: James R
authors.initials: JR
authors.lastname: Bell
authors.forename: Gabriel B
authors.initials: GB
authors.lastname: Bernasochi
authors.forename: Upasna
authors.initials: U
authors.lastname: Varma
authors.forename: Antonia J A
authors.initials: AJ
authors.lastname: Raaijmakers
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
mesh_terms: D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen
keywords: Aromatase; Ca handling; Cardiac hypertrophy; Contractile function; Estrogen; Heart; Ischemia; Testosterone