Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen plus progestagen signaling
Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen plus progestagen signaling
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DOI：
10.1007/s00109-006-0146-1
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发表时间：
2007-05-01
影响因子：
4.7
通讯作者：
Blok, L. J.
中科院分区：
文献类型：
--
作者：
Hanifi-Moghaddam, P.;Boers-Sijmons, B.;Blok, L. J.
替博龙是一种组织选择性化合物，具有雌激素、孕激素和雄激素特性的组合，被用作雌激素或雌激素加孕酮激素疗法的替代品，用于治疗与更年期和骨质疏松症相关的症状。本研究比较了因子宫内膜脱垂而接受子宫切除术的健康绝经后妇女短期（21天）接受替博龙治疗后的子宫内膜基因表达谱与单纯雌二醇（E-2）和E-2 +醋酸甲孕酮（E-2 + MPA）治疗后的子宫内膜基因表达谱。E-2治疗对子宫内膜基因表达的影响（799个基因）远高于替博龙（173个基因）或E-2 + MPA治疗（174个基因）的影响。此外，替博龙治疗后的子宫内膜基因表达谱与E-2治疗后的基因表达谱相似性较弱（重叠72个基因），与E-2 + MPA治疗后的基因表达谱相似性更低（重叠17个基因）。有趣的是，鉴定出95个替博龙特异性基因。将图谱相似性翻译为生物学过程和途径表明，er介导的下游过程，如细胞周期和细胞增殖，不受E2 + MPA的影响，受替博龙的影响较小，但受E-2的影响显著。综上所述，替博龙治疗在人子宫内膜中产生了替博龙特异性基因表达谱，其与E-2的相似性有限，与E2 + MPA诱导的基因表达谱的相似性更小。
Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E-2) and E-2 + medroxyprogesterone acetate (E-2 + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E-2 treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E-2 + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E-2 treatment (overlap 72 genes) and even less profile similarity to E-2 + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E-2. In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E-2 and even less resemblance to E2 + MPA induced profiles.