Compr Physiol. 2026 Jun;16(3):e70159. doi: 10.1002/cph4.70159.
ABSTRACT
Cardiovascular diseases remain the leading global cause of morbidity and mortality, with notable sex-specific differences in prevalence and outcomes. Increasing evidence indicates that β-adrenergic receptors (β-AR) play a central role in cardiovascular regulation and that their expression, signaling, and responsiveness are modulated by estrogen. However, the precise mechanisms underlying β-AR-estrogen interactions remain incompletely defined and highly context dependent. This mini-review summarizes current knowledge of β-AR subtypes, their cardiovascular distribution, and their signaling pathways, emphasizing how estrogen influences β-AR function across species, sexes, ages, and cardiovascular tissues. Comparative analysis of data reveals substantial heterogeneity arising from tissue specificity, receptor subtype composition, and experimental models. These differences underscore the challenges of translating preclinical findings into human physiology. Future studies integrating multi-species and sex-specific approaches, including the development of genetic knockout models and validation using human vascular cells, are essential to bridge mechanistic insights with clinical relevance. Understanding the interplay between β-AR signaling and estrogen is key to developing sex-specific strategies for the prevention and treatment of cardiovascular diseases.
PMID:42056723 | DOI:10.1002/cph4.70159