Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome

Sex differences are ubiquitous in human development,aging and disease.For example,the overwhelming majority of non-reproductive system cancers are more common in males(Mauvais-Jarvis et al.,2020),while autoimmune diseases are more common in females.Hormones,especially androgens and oestrogens,contribute to sex-biased phenotypes(Khramtsova et al.,2019).The androgen signaling pathway is also vital in the occurrence and development of various diseases.Research has demonstrated that androgen deprivation through castration surgery had a significant effect on the treatment of prostate cancer(Huggins and Hodges,2002).Recent studies have a profound understanding of the mechanism of action of androgens for therapeutic strategies(Stevanovićet al.,2024).Among them,the inhibitor of the key enzyme CYP17 for androgen synthesis,Abiraterone,has already achieved success in clinical practice(Chi et al.,2016).The main function of androgens is achieved through androgen receptors(AR),which can alter the conformation of androgens and promote its entry into the nucleus,exerting regulatory effects on transcription factors.Gao et al.constructed a single-cell transcriptome spectrum containing over 2.3 million cells based on 17 different tissues and organs of mice.Combined with multiple functional mechanism experiments,they systematically analyzed the specific role of androgens in sex differences(Li et al.,2024).