Sex Chromosome Related Dimorphism in Steroidogenic Enzymes and Androgen Receptor in Response to Testosterone Treatment: An In Vitro Study on Human Primary Skeletal Muscle Cells

    Luigi Di Luigi, Cristina Antinozzi, Guglielmo Duranti, Ivan Dimauro, Paolo Sgrò
    TLDR Chromosomal differences affect how muscle cells respond to testosterone.
    This in vitro study examined sex-chromosome-related differences in steroidogenic enzyme and androgen receptor (AR) expression in human primary skeletal muscle cells (46XY and 46XX) in response to testosterone treatment. 46XY cells exhibited higher baseline mRNA expression for 5α-reductase (5α-R2) and AR, while 46XX cells had higher aromatase (CYP-19) mRNA expression. Testosterone exposure increased AR expression and translocation at lower doses in 46XX cells compared to 46XY cells. These findings highlight significant sex-chromosome-related differences in muscle steroidogenesis and AR response, emphasizing the need to consider chromosomal disparities in clinical and therapeutic settings. The study's limitations include the use of cells from a single male and female donor, suggesting the need for further research with more biological replication.
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