Suppressed estrogen supply via extra-ovarian progesterone receptor membrane component 1 in menopause
Sang R.Lee1
Hyun Yang2
Seong Lae Jo1
Young Ho Lee1
Hye Won Lee2
Bae-keun Park1
Eui-Ju Hong1
1.College of Veterinary Medicine,Chungnam National University,Daejeon 34134,Republic of Korea2.KM Convergence Research Division,Korea Institute of Oriental Medicine,Daejeon 34054,Republic of Korea
摘要：In post-menopausal women,intra-mammary estrogen,which is converted from extra-ovarian estrone(E1),promotes the growth of breast cancer.Since the aromatase inhibitor letrozole does not suppress 17β-estradiol(E2)production from E1,high intra-mammary E1 concentrations impair letrozole's therapeutic efficacy.Progesterone receptor membrane component 1(Pgrmc1)is a non-classical progesterone receptor associated with breast cancer progression.In the present study,we introduced a Pgrmc1 heterozygous knockout(hetero KO)murine model exhibiting low Pgrmc1 expression,and observed estrogen levels and steroidogenic gene expression.Na?ve Pgrmc1 hetero KO mice exhibited low estrogen(E2 and E1)levels and low progesterone receptor(PR)expression,compared to wild-type mice.In contrast,Pgrmcl hetero KO mice that have been ovariectomized(OVX),including letrozole-treated OVX mice(OVX-letrozole),exhibited high estrogen levels and PR expression.Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase(STS).In MCF-7 cell,letrozole suppressed PR expression,but PGRMC1 knockdown increased PR and STS expression.Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited,thereby suggesting a potential therapeutic approach for letrozole resistance.
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分类号：R737.9(泌尿生殖器肿瘤)
论文发表日期：2021-05-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 228-237 )
英文信息