Sex and sex hormones in cardiac stress—Mechanistic insights

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 137; pp. 124 - 135
• Main Authors: Bell, James R., Bernasochi, Gabriel B., Varma, Upasna, Raaijmakers, Antonia J.A., Delbridge, Lea M.D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2013
• Subjects: Aromatase; Ca handling; Cardiac hypertrophy; Contractile function; Estrogen; Female; Gonadal Steroid Hormones - physiology; Heart; Heart - physiopathology; Humans; Ischemia; Male; Receptors, Androgen - metabolism; Receptors, Estrogen - metabolism; Stress, Physiological; Testosterone; Heart; Testosterone; Ischemia; Aromatase; Contractile function; Estrogen; Cardiac hypertrophy; Ca handling
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2013.05.015

•Important sex differences are evident in cardiac stress responses.•Cardiac androgen/estrogen receptor activation modulates basal contractile function.•Sex steroids exhibit complex & context dependent actions in cardiac stress.•Both estrogens and androgens can have beneficial and detrimental effects in cardiac stress scenarios.•Greater mechanistic understanding required to develop sex-specific cardiac therapies.
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 Ca2+ 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.