Estriol is an agonist of estrogen receptors (ERα and ERβ) and G protein-coupled receptor 30 (GPR30) antagonist [1]. Estriol binds to ERα/ERβ in the nucleus, inducing gene transcription and influencing cell proliferation, differentiation, and other functions [2]. Estriol is used for topical skin anti-aging and potential immunomodulatory treatments [3-4].
In SkBr3 cells, Estriol (1μM; 6d) can block the abnormal proliferation of breast cancer cells by inhibiting the GPR30-dependent signaling pathway [1]. In MDA-MB-231 cells, Estriol (1-80μM; 7d) inhibits 17β-estradiol-stimulated cell proliferation [5]. In myelin basic protein-reactive T cell, Estriol (0-50ng/mL; 16h) treatment showed a dose-dependent inhibitory effect on cell migration [6].
In pentylenetetrazol (PTZ)-kindled epilepsy mouse model, Estriol (0.005mg/kg, 0.01mg/kg; ip; single injection) treatment increases the incidence of epileptic seizures [7]. In a streptozotocin-induced type 1 diabetic mouse model, Estriol (3.5µM; iv; single injection) controls hyperglycemia through hepatic insulin synthesis [8].
References:
[1]. Lappano R, Rosano C, De Marco P, et al. Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells[J]. Molecular and cellular endocrinology, 2010, 320(1-2): 162-170.
[2]. Kim S, Liva S M, Dalal M A, et al. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis[J]. Neurology, 1999, 52(6): 1230-1230.
[3]. Ali E S, Mangold C, Peiris A N. Estriol: emerging clinical benefits[J]. Menopause, 2017, 24(9): 1081-1085.
[4]. Merrill R C. Estriol: a review[J]. Physiological reviews, 1958, 38(3): 463-480.
[5]. Girgert R, Emons G, Gründker C. Inhibition of GPR30 by estriol prevents growth stimulation of triple-negative breast cancer cells by 17β-estradiol[J]. BMC cancer, 2014, 14(1): 935.
[6]. Zang Y C Q, Halder J B, Hong J, et al. Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-κB[J]. Journal of neuroimmunology, 2002, 124(1-2): 106-114.
[7]. Ahmad A, Vohora D. Proconvulsant effects of estriol, the third estrogen, in the mouse PTZ-kindling model[J]. Neurological Sciences, 2014, 35(10): 1561-1566.
[8]. Bhattacharya S, Bank S, Maiti S, et al. The control of hyperglycemia by estriol and progesterone in alloxan induced type I diabetes mellitus mice model through hepatic insulin synthesis[J]. International Journal of Biomedical Science: IJBS, 2014, 10(1): 8.
Estriol是雌激素受体（ERα和ERβ）的激动剂和G蛋白偶联受体30（GPR30）的拮抗剂 [1]。Estriol在细胞核内与ERα/ERβ结合，诱导基因转录并影响细胞增殖、分化等功能 [2]。Estriol用于局部皮肤抗衰老和潜在的免疫调节治疗 [3-4]。
在SkBr3细胞中，Estriol（1μM；6d）可通过抑制GPR30依赖性信号通路来阻断乳腺癌细胞的异常增殖 [1]。在MDA-MB-231细胞中，Estriol（1-80μM；7d）可抑制17β-雌二醇刺激的细胞增殖 [5]。在髓鞘碱性蛋白反应性T细胞中，Estriol（0-50ng/mL；16h）处理显示出剂量依赖性的细胞迁移抑制作用 [6]。
在戊四氮（PTZ）点燃的癫痫小鼠模型中，Estriol（0.005mg/kg，0.01mg/kg;ip；单次注射）治疗可增加癫痫发作的发生率 [7]。在链脲佐菌素诱发的1型糖尿病小鼠模型中，Estriol（3.5µM；iv；单次注射）通过肝脏胰岛素合成控制高血糖 [8]。