Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Cardiology

Background:

• Hypogonadism, resulting from orchidectomy (ORX), can lead to cardiac dysfunction.
• Intracellular calcium (Ca2+) handling by cardiomyocytes is crucial for cardiac function and relaxation.

Purpose of the Study:

• To investigate the role of male sex hormones in regulating cardiac relaxation.
• To determine the impact of orchidectomy and testosterone supplementation on Ca2+-handling proteins, specifically SERCA and NCX.

Main Methods:

• Evaluation of cardiac function and relaxation in isolated ventricular trabeculae from ORX and sham-operated rats.
• Biochemical analysis of SERCA and NCX activity, protein content, and phospholamban phosphorylation in cardiac tissue.
• Assessment of testosterone's effects on these parameters.

Main Results:

• Orchidectomy significantly reduced contraction force and prolonged relaxation time (T50) in rat hearts.
• SERCA activity was decreased by 27% in ORX rats, with increased Ca2+ sensitivity, an effect prevented by testosterone.
• Testosterone partially corrected the impaired cardiac function and SERCA activity in ORX rats, while NCX function remained unaffected.

Conclusions:

• Male sex hormones play a significant role in regulating cardiac relaxation, primarily through modulation of SERCA activity.
• Testosterone deficiency impairs cardiomyocyte Ca2+ handling and cardiac function.
• Further research is needed to elucidate the precise mechanisms by which male sex hormones regulate SERCA under hypogonadal conditions.