Attenuation of 5α-Reductase-Mediated Progesterone Metabolism Promotes Differentiation of Human Endometrial Stromal Cells for the Establishment of Pregnancy

    January 2020 in “ Nihon Yakuri Gakkai nenkai yoshishu ”
    Kazumi Kawamura, Mikihiro Yoshie, Sayaha Nakajima, Tsubasa Chiba, Junya Kojima, Hirotaka Nishi, Keiichi Isaka, Kazuhiro Tamura
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    TLDR Reducing 5α-reductase activity helps endometrial cells differentiate, aiding pregnancy.
    The study investigated the role of 5α-reductase-mediated progesterone (P4) metabolism in the differentiation of human endometrial stromal cells (ESCs), which is crucial for pregnancy establishment. It was found that differentiated ESCs had higher residual P4 levels and lower levels of the P4 metabolite allopregnanolone compared to undifferentiated cells. Inhibiting 5α-reductase with dutasteride and finasteride repressed P4 metabolism and enhanced the expression of differentiation markers IGF-binding protein 1 and prolactin in P4/db-cAMP-stimulated ESCs. Additionally, the expression of the gene SRD5A1, encoding 5α-reductase type 1, was reduced in differentiated cells. This suggests that 5α-reductase-mediated P4 metabolism plays a role in increasing P4 levels to promote ESC differentiation.
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