Currently, our understanding of hormonal regulation within the female reproductive system is largely based on our knowledge of estrogen and progesterone signalling. However, while the important functions of androgens in male physiology are well known, it is also recognized that androgens play critical roles in the female reproductive system. Further, androgen signalling is altered in a variety of gynaecological conditions, including endometriosis and polycystic ovary syndrome, indicative of regulatory roles in endometrial and ovarian function. Co-regulatory mechanisms exist between different androgens, estrogens, and progesterone, resulting in a complex network of steroid hormone interactions. Evidence from animal knockout studies, in vitro experiments, and human data indicate that androgen receptor expression is cell-specific and menstrual cycle stage-dependent, with important regulatory roles in the menstrual cycle, endometrial biology, and follicular development in the ovaries. This review will discuss the expression and co-regulatory interactions of androgen receptors, highlighting the complexity of the androgen signalling pathway in the endometrium and ovaries, and the synthesis of androgens from additional alternative pathways previously disregarded as male-specific. Moreover, it will illustrate the challenges faced when studying androgens in female biology, and the need for a more in-depth, integrative view of androgen metabolism and signalling in the female reproductive system.
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http://dx.doi.org/10.1093/molehr/gaad017 | DOI Listing |
Cancer Diagn Progn
January 2025
Department of Urology, Showa University School of Medicine, Tokyo, Japan.
Background/aim: Although multiple treatments are available for metastatic castration-resistant prostate cancer, data to determine the optimal treatment sequence are limited. This study aimed to investigate the current status of drug therapy for castration-resistant prostate cancer and clarify the sequential treatment in actual clinical practice.
Patients And Methods: This retrospective study included 425 patients diagnosed with castration-resistant prostate cancer at Showa University Hospital and affiliated hospitals between January 2014 and December 2021, who were treated with any of the following four drugs: novel androgen receptor signal inhibitors (abiraterone acetate and enzalutamide) and anticancer drugs (docetaxel and cabazitaxel).
Endocr Relat Cancer
January 2025
S Dehm, Masonic Cancer Center, University of Minnesota, Minneapolis, United States.
Treatment for castration-resistant prostate cancer (CRPC) primarily involves the suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling, or lineage plasticity that drives emergence of AR-independent phenotypes.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Background: The increased incidence of androgenic alopecia (AGA) causes adverse physiological and psychological effects on people of all genders. The hair follicle stem cells (HFSCs) have displayed clinical improvements on AGA. However, the molecular mechanism of HFSCs against AGA remains elusive.
View Article and Find Full Text PDFEMBO Mol Med
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
Aggressive prostate cancer (PCa) variants associated with androgen receptor signaling inhibitor (ARSI) resistance and metastasis remain poorly understood. Here, we identify the axon guidance semaphorin receptor PlexinD1 as a crucial driver of cancer aggressiveness in metastatic castration-resistant prostate cancer (CRPC). High PlexinD1 expression in human PCa is correlated with adverse clinical outcomes.
View Article and Find Full Text PDFClin Cancer Res
January 2025
University of Minnesota, Minneapolis, United States.
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