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Sex Differences in Trace Amine-Associated Receptor Signalling
Lesha Pretorius1, Carine Smith2
1Department of Medicine, Stellenbosch University, Parow, South Africa.
Handbook of Experimental Pharmacology
|July 16, 2026
Summary
Trace amine-associated receptor (TAAR) research for neuropsychiatric diseases often ignores sex differences. This review examines TAAR1, TAAR5, and TAAR8, highlighting sex-specific expression and function to improve therapeutic development for all.
Area of Science:
- Neuropharmacology and Translational Neuroscience
- Investigating the biological underpinnings of neuropsychiatric disorders and developing targeted therapies.
Background:
- Current drug discovery for trace amine-associated receptors (TAARs) in neuropsychiatric conditions predominantly uses male subjects or aggregates sex data.
- This approach overlooks potential sex-specific mechanisms, hindering a comprehensive understanding of TAAR involvement in these diseases.
- Sex bias is a significant factor in neuropsychiatric disorders, yet its impact on TAAR pathways remains under-explored.
Purpose of the Study:
- To review and summarize reported sex differences in the expression and function of TAAR1, TAAR5, and TAAR8.
- To explore the influence of other signaling pathway components, including TAAR ligands and estrogen, on TAAR function.
- To critically assess the likelihood of significant sex differences in TAAR signaling and provide recommendations for future research.
Main Methods:
- Comprehensive literature search focusing on TAAR1, TAAR5, and TAAR8.
- Analysis of studies reporting sex-specific data on TAAR expression and function across species.
- Inclusion of research on TAAR ligands, signaling pathway modulators, and the role of estrogen.
Main Results:
- Existing research on TAARs in neuropsychiatric disease largely neglects sex as a variable, limiting understanding of sex-specific effects.
- Data on sex differences in TAAR expression and function are sparse but suggest potential variations that warrant further investigation.
- Estrogen may play a role in modulating TAAR activity, indicating a complex interplay between hormonal status and TAAR signaling.
Conclusions:
- Significant sex differences in TAAR signaling are plausible and require dedicated research to elucidate.
- Future TAAR-focused therapeutic development must incorporate sex as a biological variable to ensure equitable efficacy and safety for both males and females.
- Prioritizing research on sex-specific TAAR mechanisms is crucial for advancing personalized medicine in neuropsychiatric disorders.
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