Endogenous Metabolite; steroid hormone

雌二醇（10 nM，7 天）可刺激神经元发育并增强人子宫内膜干细胞 (hEnSC) 的轴突分支[1]。雌二醇（17β-雌二醇，10 nM，7 天）可增强 hEnSC 生成的神经元样细胞中神经元样细胞标记物（Tuj-1、巢蛋白和 NF-H）的表达 [1]。

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人子宫内膜干细胞（hEnSCs）可以分化为各种神经细胞类型，被认为是神经组织工程和再生医学的合适细胞群。考虑到激素、生长因子和神经系统中其他因素之间的不同相互作用，已经提出了几种分化方案来引导hEnSCs向特定的神经细胞分化。17β-estradiol (E2)/17β-雌二醇（E2）在神经系统的发育、成熟和功能过程中起着重要作用。本研究首次基于神经基因和蛋白质的表达水平，研究了17β-雌二醇（雌激素，E2）对hEnSCs神经分化的影响。在这方面，在17β-雌二醇存在或不存在的情况下，hEnSCs在暴露于视黄酸（RA）、表皮生长因子（EGF）和成纤维细胞生长因子-2（FGF2）后分化为神经元样细胞。大多数细胞显示多极形态。在所有组中，巢蛋白、Tuj-1和NF-H（神经丝重多肽）（作为神经特异性标志物）的表达水平在14天内都有所增加。根据免疫荧光（IF）和实时PCR分析的结果，与无雌激素组相比，雌激素治疗组的神经元特异性标记物表达更多。这些发现表明，17β-雌二醇和其他生长因子可以在hEnSCs的神经元分化过程中刺激和上调神经标志物的表达。此外，我们的研究结果证实，hEnSCs可以成为神经退行性疾病和神经组织工程细胞治疗的合适细胞来源[1]。

雌二醇（1 nM，来自 FBN-ARO-KO 小鼠的海马切片）可恢复 LTP 振幅 [1]。雌二醇（0.0167 mg，皮下植入）可纠正 FBN-ARO-KO 小鼠的分子和功能异常[1]。

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神经元来源的17β-estradiol (E2)/17β-雌二醇（E2）的耗竭导致树突棘密度显著降低。 神经元来源的E2的缺失导致突触数量显著减少。 FBN-ARO-KO小鼠的功能性突触可塑性显著受损，并通过急性E2治疗得到挽救。 体内外源性E2替代可以挽救FBN-ARO-KO小鼠的分子和功能缺陷。 [2]

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17β-雌二醇（E2）是由雄激素通过芳香化酶的作用产生的。众所周知，E2是在大脑的神经元中产生的，但它在大脑中的确切功能尚不清楚。在这里，我们使用前脑神经元特异性芳香化酶敲除（FBN-ARO-KO）小鼠模型来耗竭小鼠前脑中神经元衍生的E2，从而阐明其功能。与FLOX对照组相比，FBN-ARO-KO小鼠的芳香化酶和前脑E2水平降低了70-80%。雄性和雌性FBN-ARO-KO小鼠在前脑棘和突触密度以及海马依赖性空间参考记忆、识别记忆和情境恐惧记忆方面表现出明显的缺陷，但运动功能和焦虑水平正常。通过外源性体内E2给药恢复前脑E2水平能够挽救FBN-ARO-KO小鼠的分子和行为缺陷。此外，使用FBN-ARO-KO海马切片的体外研究表明，虽然长时程增强（LTP）的诱导是正常的，但振幅显著降低。有趣的是，体外急性E2治疗可以完全挽救LTP缺陷。机制研究表明，FBN-ARO-KO小鼠海马和大脑皮层中的快速激酶（AKT、ERK）和CREB-BDNF信号传导受损。此外，海马FBN-ARO-KO切片中LTP的急性E2救援可以通过施用MEK/ERK抑制剂来阻断，这进一步表明ERK快速信号传导在神经元E2效应中起着关键作用。总之，这些发现为神经元衍生的E2在调节男性和女性大脑的突触可塑性和认知功能方面发挥关键作用提供了证据。

对于体外17β-estradiol (E2)救援实验，将E2溶解在DMSO中，在含氧ACSF中稀释至工作浓度（1nm）（Di Mauro等人，2015）。实验中还包括DMSO（0.001%）载体对照。此外，MEK抑制剂U0126（Cell Signaling Technology，目录#9903S，10μm）也溶解在DMSO中，并在含氧ACSF中稀释至工作浓度。U0126与E2联合用药。在应用刺激方案前20分钟的所有记录期内应用药物。[2]

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17β-estradiol (E2)水平的测量。[2]
如前所述，使用高灵敏度ELISA试剂盒测量海马CA1、皮质和血清中的17β-estradiol (E2)/17β-雌二醇（E2）水平（Zhang等人，2014）。简而言之，将100μl样品加入涂有驴抗羊多克隆抗体的适当孔的底部。随后，向E2中加入50μl E2偶联物，然后加入50μl绵羊多克隆抗体。然后将平板密封，在室温下以约500rpm的摇动速度孵育2小时。每次用400μl洗涤缓冲液洗涤3次后，将200μl pNpp底物加入每个孔中，在不摇动的情况下在室温下孵育1小时。然后，向每个孔中加入50μl终止溶液，在405nm处读取光密度。

细胞分化测定[1]
细胞类型：从人类子宫内膜组织中分离出人类子宫内膜干细胞 (hEnSC)
测试浓度： 10 nM
孵化持续时间：7天
实验结果：增加神经突数量，包括神经分化和神经突分支。

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免疫荧光[1]
细胞类型：从人类子宫内膜组织中分离出的人类子宫内膜干细胞 (hEnSC)
测试浓度： 10 nM
孵育时间：7天
实验结果：神经标记物（Tuj-1、巢蛋白和NF-H）阳性细胞的百分比增加62.2分别为±1.3%、71.5±4%和51.2±1.5%。

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hEnSCs的神经元分化[1]
为了诱导神经元分化，将约3×10~4个hEnSCs接种在24孔培养板的每个孔上，并在14天内与两种不同的分化培养基一起孵育。细胞最初在37°C下用含有1%Pen-Strep和10%FBS的DMEM/F12完整培养基孵育24小时。在第一组中，为了诱导hEnSCs的神经元分化，我们用第一步诱导培养基（含有EGF和FGF2的DMEM/F12[每种浓度为20ng/ml]和B27[1%]）代替培养基7天。为了继续神经元分化，随后将细胞暴露于第二步诱导培养基（DMEM/F12，补充了1%ITS、0.5µM RA和20ng/ml FGF2）中7天。在第二组中，在初始孵育24小时后，用第一步诱导培养基（含有EGF和FGF2的DMEM/F12，每种培养基20 ng/ml浓度]和B27[1%]）处理7天，20 ng/ml FGF2和10 nM17β-雌二醇（E2）[Kang等人，2007]）直至第14天。对照组的细胞在添加了1%Pen-Strep和10%FBS的DMEM/F12存在下在TCP上培养14天。所有培养基每2天更换一次（图1）。

Animal/Disease Models: FBN-ARO-KO Mice[2]
Doses: 1 nM
Route of Administration: Treated for the hippocampal slices
Experimental Results: Rescued long-term potentiation (LTP) amplitude of both male and female mice.

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Animal/Disease Models: FBN-ARO-KO Mice [2]
Doses: 0.0167 mg
Route of Administration: Alzet minipumps with Estradiol (implanted sc), examined 7 days after minipump implantation.
Experimental Results: Restored hippocampal and cortical E2 levels to 93%, phosphorylation of AKT, ERK and CREB in the hippocampus and cortex to 90-95%, BDNF level to 80-90%, restored both synaptophysin and PSD95 in the forebrain. Rescued the spatial learning and memory defects.

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n vivo 17β-estradiol (E2) rescue experiment. [2]
Three-month-old ovx female mice were used in this experiment, which were divided into four groups: FLOX + placebo, FLOX + E2, FBN-ARO-KO + placebo, and FBN-ARO-KO + E2. Alzet minipumps osmotic minipumps; model 1007D, 7 d release; Durect) with placebo or E2 (0.0167 mg) were implanted subcutaneously in the upper midback region at the time of ovariectomy. The dose of E2 used here yields stable serum levels of 26.52 ± 0.89 pg/ml, which represents a physiological diestrus II–proestrus level of E2 (Nelson et al., 1981). Molecular and functional endpoints were examined 7 d after minipump implantation.

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Experimental design and statistical analyses. [2]
All quantitative analyses were performed on age-matched FLOX control and FBN-ARO-KO mice. Except for the in vivo 17β-estradiol (E2) rescue experiment, both male and female mice were used. Only female mice were used for in vivo E2 replacement. For behavioral tests, 8–10 mice were used for each group; otherwise, 4–6 samples from each group were analyzed. SigmaStat 3.5 software was used to analyze all data. Data represented in bar graphs were expressed as mean ± SE. A Student's t test was performed when only comparing two groups. Statistical data from the Barnes maze training trial, fear acquisition test, electrophysiological measurements, and part of the in vivo E2 replacement experiments requiring multiple groups comparisons were analyzed with two-way ANOVA followed by Tukey's all pairwise comparisons test to determine group differences. A value of p < 0.05 was considered statistically significant.

Absorption, Distribution and Excretion
The absorption of several formulations of estradiol is described below: Oral tablets and injections First-pass metabolism in the gastrointestinal tract rapidly breaks down estradiol tablets before entering the systemic circulation. The bioavailability of oral estrogens is said to be 2-10% due to significant first-pass effects. The esterification of estradiol improves the administration (such as with estradiol valerate) or to sustain release from intramuscular depot injections (including estradiol cypionate) via higher lipophilicity. After absorption, the esters are cleaved, which leads to the release of endogenous estradiol, or 17β-estradiol. Transdermal preparations The transdermal preparations slowly release estradiol through intact skin, which sustains circulating levels of estradiol during a 1 week period of time. Notably, the bioavailability of estradiol after transdermal administration is about 20 times higher than after oral administration. Transdermal estradiol avoids first pass metabolism effects that reduce bioavailability. Administration via the buttock leads to a Cmax of about 174 pg/mL compared to 147 pg/mL via the abdomen. Spray preparations After daily administration, the spray formulations of estradiol reach steady state within 7-8 days. After 3 sprays daily, Cmax is about 54 pg/mL with a Tmax of 20 hours. AUC is about 471 pg•hr/mL. Vaginal ring and cream preparations Estradiol is efficiently absorbed through the mucous membranes of the vagina. The vaginal administration of estrogens evades first-pass metabolism. Tmax after vaginal ring delivery ranges from 0.5 to 1 hour. Cmax is about 63 pg/mL. The vaginal cream preparation has a Cmax of estradiol (a component of Premarin vaginal estrogen conjugate cream) was a Cmax of 12.8 ± 16.6 pg/mL, Tmax of 8.5 ± 6.2 hours, with an AUC of 231 ± 285 pg•hr/mL.
Estradiol is excreted in the urine with both glucuronide and sulfate conjugates.
Estrogens administered exogenously distribute in a similar fashion to endogenous estrogens. They can be found throughout the body, especially in the sex hormone target organs, such as the breast, ovaries and uterus.
In one pharmacokinetic study, the clearance of orally administered micronized estradiol in postmenopausal women was 29.9±15.5 mL/min/kg. Another study revealed a clearance of intravenously administered estradiol was 1.3 mL/min/kg.
Estrogens used in therapeutics are well absorbed through the skin, mucous membranes, and the gastrointestinal (GI) tract. The vaginal delivery of estrogens circumvents first-pass metabolism.
The Estradiol Transdermal System Continuous Delivery (Once-Weekly) continuously releases estradiol which is transported across intact skin leading to sustained circulating levels of estradiol during a 7 day treatment period. The systemic availability of estradiol after transdermal administration is about 20 times higher than that after oral administration. This difference is due to the absence of first-pass metabolism when estradiol is given by the transdermal route.
In a Phase I study of 14 postmenopausal women, the insertion of ESTRING (estradiol vaginal ring) rapidly increased serum estradiol (E2) levels. The time to attain peak serum estradiol levels (Tmax) was 0.5 to 1 hour. Peak serum estradiol concentrations post-initial burst declined rapidly over the next 24 hours and were virtually indistinguishable from the baseline mean (range: 5 to 22 pg/mL). Serum levels of estradiol and estrone (E1) over the following 12 weeks during which the ring was maintained in the vaginal vault remained relatively unchanged
Table: PHARMACOKINETIC MEAN ESTIMATES FOLLOWING SINGLE ESTRING APPLICATION [Table#4649]

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Metabolism / Metabolites
Exogenously administered estrogens are metabolized in the same fashion as endogenous estrogens. Metabolic transformation occurs primarily in the liver and intestine. Estradiol is metabolized to estrone, and both are converted to estriol, which is later excreted in the urine. Sulfate and glucuronide conjugation estrogens also take place in the liver. Biliary secretion of metabolic conjugates are released into the intestine, and estrogen hydrolysis in the gut occurs, followed by reabsorption. The CYP3A4 hepatic cytochrome enzyme is heavily involved in the metabolism of estradiol. CYP1A2 also plays a role.
Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.
Variations in estradiol metabolism ... depend upon the stage of the menstrual cycle ... In general, the hormone undergoes rapid hepatic biotransformation with a plasma half-life measured in minutes.
Estradiol is primarily converted ... to estriol, which is the major urinary metabolite. A variety of sulfate and glucuronide conjugates also are excreted in the urine.
The metabolism of estradiol-17beta and estrone is similar in rats and in humans, in that both species transform these steroids mainly by (aromatic) 2-hydroxylation, and also by 16alpha-hydroxylation. Glucuronides of the various metabolites are excreted in the bile. Differences in the metabolism of estrogens by humans and rats lie mostly in the type of conjugation. A relatively large proportion of administered estrone, estradiol-17beta and estriol is transformed in rats to metabolites oxygenated both at C-2 and C-16. When estriol is administered to rats, glucuronides and, to a lesser extent, sulfates of 16-ketooestradiol and of 2- and 3-methyl ethers of 2-hydroxyoestriol and 2-hydroxy-16-ketooestradiol are excreted in the bile. In contrast, hydroxylations at C-6 or C-7 of ring B of estradiol-17beta and estrone are a minor pathway in rats. 2-Hydroxyoestrogens ('catechol estrogens') are further transformed by various routes, including covalent binding to proteins.
For more Metabolism/Metabolites (Complete) data for ESTRADIOL (8 total), please visit the HSDB record page.
17-beta-estradiol has known human metabolites that include 2-hydroxyestradiol, 4-Hydroxyestradiol, 17-beta-Estradiol-3-glucuronide, and 17-beta-Estradiol glucuronide.
Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.
Route of Elimination: Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.
Half Life: 36 hours

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Biological Half-Life
The terminal half-lives for various estrogen products post oral or intravenous administration has been reported to range from 1-12 hours. One pharmacokinetic study of oral estradiol valerate administration in postmenopausal women revealed a terminal elimination half-life of 16.9 ± 6.0 h. A pharmacokinetic study of intravenous estradiol administration in postmenopausal women showed an elimination half-life of 27.45 ± 5.65 minutes. The half-life of estradiol appears to vary by route of administration.
... After oral administration ... the terminal half life was 20.1 hr ...

Toxicity Summary
Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.

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Interactions
Estrogens may interfere with the effects of bromocriptine; dosage adjustment may be necessary. /Estrogens/
A combination of testosterone and estradiol-B17 after treatment with methylnitrosurea also resulted in the development of adenocarciomas of the prostate.
Concurrent use with estrogens may increase calcium absorption and exacerbate nephrolithiasis in susceptible individuals; this can be used to therapeutic advantage to increase bone mass. /Estrogens/
Concurrent use /of glucocorticoid corticosteroids/ with estrogens may alter the metabolism and protein binding of the glucocorticoids, leading to decreased clearance, increased elimination half-life, and increased therapeutic and toxic effects of the glucocorticoids; glucocorticoid dosage adjustment may be required during and following concurrent use. /Estrogens/
For more Interactions (Complete) data for ESTRADIOL (11 total), please visit the HSDB record page.

[1]. Elham Hasanzadeh. Defining the role of 17β-estradiol in human endometrial stem cells differentiation into neuron-like cells. Cell Biol Int. 2021 Jan;45(1):140-153.

[2]. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory. J Neurosci. 2019 Apr 10;39(15):2792-2809.

Therapeutic Uses
Estradiol tablets are indicated in the treatment of moderate to severe vasomotor symptoms associated with the menopause. /Included in US product label/
Estradiol tablets are indicated in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. /Included in US product label/
Estradiol tablets are indicated in the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. /Included in US product label/
Estradiol tablets are indicated in the treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease. /Included in US product label/
For more Therapeutic Uses (Complete) data for ESTRADIOL (7 total), please visit the HSDB record page.

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Drug Warnings
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER- Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than "synthetic" estrogens at equivalent estrogen doses.
CARDIOVASCULAR AND OTHER RISKS- Estrogens with or without progestins should not be used for the prevention of cardiovascular disease.
The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo.
The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy.
For more Drug Warnings (Complete) data for ESTRADIOL (48 total), please visit the HSDB record page.

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Pharmacodynamics
Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia). Estradiol has also been shown to exert favorable effects on bone density by inhibiting bone resorption. Estrogen appears to inhibit bone resorption and may have beneficial effects on the plasma lipid profile. Estrogens cause an increase in hepatic synthesis of various proteins, which include sex hormone binding globulin (SHBG), and thyroid-binding globulin (TBG). Estrogens are known to suppress the formation of follicle-stimulating hormone (FSH) in the anterior pituitary gland. **A note on hyper-coagulable state, cardiovascular health, and blood pressure** Estradiol may cause an increased risk of cardiovascular disease, DVT, and stroke, and its use should be avoided in patients at high risk of these conditions. Estrogen induces a hyper-coagulable state, which is also associated with both estrogen-containing oral contraceptive (OC) use and pregnancy. Although estrogen causes an increase in levels of plasma renin and angiotensin. Estrogen-induced increases in angiotensin, causing sodium retention, which is likely to be the mechanism causing hypertension after oral contraceptive treatment.

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17β-estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but its precise functions in the brain are unclear. Here, we used a forebrain-neuron-specific aromatase knock-out (FBN-ARO-KO) mouse model to deplete neuron-derived E2 in the forebrain of mice and thereby elucidate its functions. FBN-ARO-KO mice showed a 70-80% decrease in aromatase and forebrain E2 levels compared with FLOX controls. Male and female FBN-ARO-KO mice exhibited significant deficits in forebrain spine and synaptic density, as well as hippocampal-dependent spatial reference memory, recognition memory, and contextual fear memory, but had normal locomotor function and anxiety levels. Reinstating forebrain E2 levels via exogenous in vivo E2 administration was able to rescue both the molecular and behavioral defects in FBN-ARO-KO mice. Furthermore, in vitro studies using FBN-ARO-KO hippocampal slices revealed that, whereas induction of long-term potentiation (LTP) was normal, the amplitude was significantly decreased. Intriguingly, the LTP defect could be fully rescued by acute E2 treatment in vitro Mechanistic studies revealed that FBN-ARO-KO mice had compromised rapid kinase (AKT, ERK) and CREB-BDNF signaling in the hippocampus and cerebral cortex. In addition, acute E2 rescue of LTP in hippocampal FBN-ARO-KO slices could be blocked by administration of a MEK/ERK inhibitor, further suggesting a key role for rapid ERK signaling in neuronal E2 effects. In conclusion, the findings provide evidence of a critical role for neuron-derived E2 in regulating synaptic plasticity and cognitive function in the male and female brain.SIGNIFICANCE STATEMENT The steroid hormone 17β-estradiol (E2) is well known to be produced in the ovaries in females. Intriguingly, forebrain neurons also express aromatase, the E2 biosynthetic enzyme, but the precise functions of neuron-derived E2 is unclear. Using a novel forebrain-neuron-specific aromatase knock-out mouse model to deplete neuron-derived E2, the current study provides direct genetic evidence of a critical role for neuron-derived E2 in the regulation of rapid AKT-ERK and CREB-BDNF signaling in the mouse forebrain and demonstrates that neuron-derived E2 is essential for normal expression of LTP, synaptic plasticity, and cognitive function in both the male and female brain. These findings suggest that neuron-derived E2 functions as a novel neuromodulator in the forebrain to control synaptic plasticity and cognitive function. [2]

C18H24O2

272.38

272.177

C, 79.37; H, 8.88; O, 11.75

50-28-2

Alpha-Estradiol;57-91-0;Estradiol (Standard);50-28-2;Estradiol-d3;79037-37-9;Estradiol-d4;66789-03-5;Estradiol-d5;221093-45-4;Estradiol-13C2;82938-05-4;Estradiol (cypionate);313-06-4;Estradiol benzoate;50-50-0;Estradiol enanthate;4956-37-0;Estradiol hemihydrate;35380-71-3;Estradiol-d2;53866-33-4;Estradiol-13C6;Estradiol-d2-1;3188-46-3;rel-Estradiol-13C6; 979-32-8 (valerate); 113-38-2 (dipropionate); 57-63-6 (ethinyl); 172377-52-5 (sulfamate); 3571-53-7 (undecylate)

5757

White to off-white solid powder

1.2±0.1 g/cm3

445.9±45.0 °C at 760 mmHg

173ºC

209.6±23.3 °C

0.0±1.1 mmHg at 25°C

1.599

4.13

40.46

2

2

0

20

382

5

O([H])[C@@]1([H])C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4C([H])=C(C([H])=C([H])C=4[C@@]3([H])C([H])([H])C([H])([H])[C@@]21C([H])([H])[H])O[H]

VOXZDWNPVJITMN-ZBRFXRBCSA-N

InChI=1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1

(8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (9.18 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.5 mg/mL (9.18 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (9.18 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.08 mg/mL (7.64 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.08 mg/mL (7.64 mM)(饱和度未知) in ≥ 2.5 mg/mL (5.35 mM) (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 6 中的溶解度: 12.5 mg/mL (45.89 mM) in Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。