Estrone is one of the three major endogenous estrogens, the others being estradiol and estriol[1]. Estrone is synthesized from cholesterol and is primarily secreted by the gonads, but can also be formed by adrenal androgens in adipose tissue[2]. Estrone is an agonist of the estrogen receptor[3]. Estrone can effectively activate multiple signaling and functional responses in pituitary cells at low physiological concentrations[4].
In vitro, treatment of human endothelial colony-forming cells (hECFCs) with Estrone (0-1µM) for 24h significantly promoted cell proliferation at concentrations of 1nM and 10nM, and inhibited proliferation at a concentration of 1µM[5]. Treatment of bone progenitor cells with Estrone (10nM) upregulated the expression of estrogen receptor α (ER-α) and estrogen receptor β (ER-β), but downregulated the expression of osteopontin (OPN)[6]. Estrone (10-3-105nM) treated mouse colon cancer MC38 cells for 24-72h inhibited cell growth in a dose- and time-dependent manner[7].
In vivo, subcutaneous injection of Estrone (0.5mg/kg) in rats with traumatic brain injury reduced cortical lesion volume and neuronal damage, reduced the level of TUNEL-positive staining in the cerebral cortex, reduced the number of TUNEL-positive cells in the corpus callosum, and reduced the cortical level of β-amyloid protein after brain injury[8].
References:
[1] Bennink H J T C. Are all estrogens the same?[J]. Maturitas, 2004, 47(4): 269-275.
[2] Tchernof A, Mansour M F, Pelletier M, et al. Updated survey of the steroid-converting enzymes in human adipose tissues[J]. The Journal of steroid biochemistry and molecular biology, 2015, 147: 56-69.
[3] Eyster K M. The estrogen receptors: an overview from different perspectives[J]. Estrogen Receptors: Methods and Protocols, 2016: 1-10.
[4] Watson C S, Jeng Y J, Kochukov M Y. Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation[J]. The FASEB Journal, 2008, 22(9): 3328.
[5] Ivory A, Greene A S. Distinct roles of estrone and estradiol in endothelial colony‐forming cells[J]. Physiological Reports, 2023, 11(19): e15818.
[6] Park J B. Effects of low doses of estrone on the proliferation, differentiation and mineralization of osteoprecursor cells[J]. Experimental and Therapeutic Medicine, 2012, 4(4): 681-684.
[7] Motylewska E, Mełeń-Mucha G. Estrone and progesterone inhibit the growth of murine MC38 colon cancer line[J]. The Journal of steroid biochemistry and molecular biology, 2009, 113(1-2): 75-79.
[8] Gatson J W, Liu M M, Abdelfattah K, et al. Estrone is neuroprotective in rats after traumatic brain injury[J]. Journal of neurotrauma, 2012, 29(12): 2209-2219.
Estrone是三种主要的内源性雌激素之一，其他是雌二醇和雌三醇[1]。Estrone是由胆固醇合成的，主要由性腺分泌，也可以由脂肪组织中的肾上腺雄激素形成[2]。Estrone是雌激素受体的激动剂[3]。Estrone在低生理浓度下能够有效地激活垂体细胞中的多种信号传导和功能反应[4]。
在体外，Estrone（0-1µM）处理人内皮集落形成细胞（hECFCs）细胞24h，在1nM和10nM浓度下显著促进了细胞增殖，1µM的浓度下抑制了增殖[5]。Estrone（10nM）处理骨前体细胞，上调了雌激素受体α（ER-α）和雌激素受体β（ER-β）的表达，但下调了骨桥蛋白（OPN）的表达[6]。Estrone（10-3-105nM）处理小鼠结肠癌MC38细胞24-72h，以剂量和时间依赖性方式抑制了细胞的生长[7]。
在体内，Estrone（0.5mg/kg）通过皮下注射治疗创伤性脑损伤大鼠，减少了皮质病变体积和神经元损伤，降低了大脑皮层TUNEL阳性染色的水平，减少了胼胝体中TUNEL阳性细胞的数量，降低了脑损伤后β-淀粉样蛋白的皮质水平[8]。