美雌醇是一种效力适中的合成雌激素，与 17β-雌二醇相比，在肝癌细胞培养物中表现出更高的稳定性 [3]。在六天内，美雌醇 (10 μM) 可以将 ER 阳性 MCF-7 WS8 细胞的增殖速度提高至对照水平的 250%。他莫昔芬可以部分逆转这种生长刺激。然而，与对照细胞相比，对 Hep G2 肝癌细胞使用美雌醇（10 μM；6 天）可使 Hep 3B 细胞的发育减少 40%。单独使用美雌醇或与他莫昔芬联合使用可以阻止细胞增殖。此外，他莫昔芬和联合治疗对生长抑制具有累积效应[2]。

Mestranol (0.2 mg/kg) 导致大鼠中表达谷胱甘肽 S-转移酶 (PGST) 的 AHF 所占据的肝脏百分比增加。与对照组相比，美雌醇给药增加了局灶性肝细胞标记指数，在较低剂量下有趋势，在较高剂量下有显着差异。与单独使用相应浓度的美雌醇观察到的结果相比，美雌醇（0.02 mg/kg 和 0.2 mg/kg 饮食）导致非焦点标记指数降低。与仅给予基础饮食的大鼠相比，美雌醇显着增加了未参加实验的大鼠的非局灶性肝标记指数。美雌醇 (50 mg/100 g b.wt.) 可显着减少大鼠额叶皮层和孤束核 (NTS) 中 α-2-肾上腺素受体的表观数量，而 α-1 和 α 的表观数量-2-肾上腺素受体在蓝斑处被抑制。

Absorption, Distribution and Excretion
Mestranol binds poorly to the estrogen receptor and its estrogenic effect is due to its rapid demethylation in the liver to form ethinylestradiol; however, demethylation is not complete and more mestranol must be administered than ethinylestradiol to achieve similar effects.
The excretion of metabolites in urine ranged from 10-27%; that of ethinyloestradiol metabolites ranges from 36-54%. When position 2 or 4 of the mestranol molecule is tritiated or marked with (14)C, between 14-45% of the radioactivity is released into the body water.

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Metabolism / Metabolites
Mestranol is rapidly absorbed and extensively metabolised to ethinylestradiol. Ethinylestradiol is rapidly and well absorbed from the gastro-intestinal tract but is subject to some first-pass metabolism in the gut-wall. Compared to many other estrogens it is only slowly metabolized in the liver. Excretion is via the kidneys with some appearing also in the feces.
In the body it undergoes rapid hepatic demethylation to ethinyl estradiol, which is its active form. /Estrogens/
Mestranol, the 3-methyl ether of ethinyloestradiol, is more lipophilic than ethinyloestradiol and has a greater affinity for adipose tissues, as shown by experiments in rats. Mestranol itself does not bind significantly to estrogen receptors at the sites of their antifertility action; its hormonal effectiveness relies on transformation to ethinyloestradiol. About 35% of a mestranol dose is transformed into ethinyloestradiol in rats, 61% in mice, 56% in rabbits and 54% in man. The demethylated portion then follows the pathways for ethinyloestradiol that are typical for the particular species, e.g., 2-hydroxylation in rats and D-homoannulation in rabbits and guinea-pigs. Mestranol is also demethylated to ethinylestradiol in non-human primates.
The metabolism of mestranol in humans is closely related to that of ethinyloestradiol. Mestranol is transformed to ethinyloestradiol by demethylation: after i.v. administration of (14)C-mestranol to human volunteers, about 50% of the dose is demethylated to ethinylestradiol. The main compound found in plasma is ethinyloestradiol-3-sulfate.
For more Metabolism/Metabolites (Complete) data for MESTRANOL (6 total), please visit the HSDB record page.
Mestranol has known human metabolites that include ethinylestradiol.

[1]. Affinity of ethynyl-estradiol and mestranol for the uterine estrogen receptor and for the microsomal mixed function oxidase of the liver. J Steroid Biochem. 1973 Mar;4(2):121-8.

[2]. Pharmacokinetics of ethinyl estradiol and mestranol. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2114-9.

[3]. Tamoxifen inhibits hepatoma cell growth through an estrogen receptor independent mechanism. J Hepatol. 1995 Dec;23(6):712-9.

Mestranol can cause cancer according to an independent committee of scientific and health experts.
Mestranol is a terminal acetylenic compound that is (17alpha)-17-ethynylestra-1(10),2,4-triene substituted by a methoxy group at position 3 and a hydroxy group at position 17. It has a role as a prodrug and a xenoestrogen. It is a 17beta-hydroxy steroid, a terminal acetylenic compound and an aromatic ether. It is functionally related to a 17beta-estradiol.
The 3-methyl ether of ethinyl estradiol. It must be demethylated to be biologically active. It is used as the estrogen component of many combination ORAL contraceptives.
Mestranol is an Estrogen. The mechanism of action of mestranol is as an Estrogen Receptor Agonist.
Mestranol has been reported in Cunninghamella elegans with data available.
Mestranol is a semisynthetic estrogen. Metabolized by the liver to ethynyl estradiol, mestranol serves as the estrogen component in several combination oral contraceptives. (NCI04)
The 3-methyl ether of ethinyl estradiol. It must be demethylated to be biologically active. It is used as the estrogen component of many combination ORAL contraceptives.
The 3-methyl ether of ETHINYL ESTRADIOL. It must be demethylated to be biologically active. It is used as the estrogen component of many combination ORAL CONTRACEPTIVES.

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Drug Indication
Mestranol was used as one of the first oral contraceptives.

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Mechanism of Action
Mestranol is the 3-methyl ether of ethinylestradiol. Ethinylestradiol, is a synthetic derivative of estradiol. Ethinylestradiol is orally bio-active and the estrogen used in almost all modern formulations of combined oral contraceptive pills. It binds to (and activates) the estrogen receptor. Mestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70%. Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
The mode of action of Norinyl-1 is similar to that of other progestogen/estrogen oral contraceptives and includes the inhibition of ovulation, the thickening of cervical mucus so as to constitute a barrier to sperm and the rendering of the endometrium unreceptive to implantation. Such activity is exerted through a combined effect on one or more of the following: hypothalamus, anterior pituitary, ovary, endometrium and cervical mucus.
Estrogens have an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. Biologic response is initiated when estrogen binds to a ligand-binding domain of the estrogen receptor resulting in a conformational change that leads to gene transcription through specific estrogen response elements (ERE) of target gene promoters; subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains (ie, AF-1 and AF-2) of the receptor. The estrogen receptor also mediates gene transcription using different response elements (ie, AP-1) and other signal pathways. Recent advances in the molecular pharmacology of estrogen and estrogen receptors have resulted in the development of selective estrogen receptor modulators (eg, clomiphene, raloxifene, tamoxifen, toremifene), agents that bind and activate the estrogen receptor but that exhibit tissue-specific effects distinct from estrogen. Tissue-specific estrogen-agonist or -antagonist activity of these drugs appears to be related to structural differences in their estrogen receptor complex (eg, specifically the surface topography of AF-2 for raloxifene) compared with the estrogen (estradiol)-estrogen receptor complex. A second estrogen receptor also has been identified, and existence of at least 2 estrogen receptors (ER-alpha, ER-beta) may contribute to the tissue-specific activity of selective modulators. While the role of the estrogen receptor in bone, cardiovascular tissue, and the CNS continues to be studied, emerging evidence indicates that the mechanism of action of estrogen receptors in these tissues differs from the manner in which estrogen receptors function in reproductive tissue. /Estrogen General Statement/
Intracellular cytosol-binding proteins for estrogens have been identified in estrogen-responsive tissues including the female genital organs, breasts, pituitary, and hypothalamus. The estrogen-binding protein complex (ie, cytosol-binding protein and estrogen) distributes into the cell nucleus where it stimulates DNA, RNA, and protein synthesis. The presence of these receptor proteins is responsible for the palliative response to estrogen therapy in women with metastatic carcinoma of the breast. /Estrogen General Statement/
Estrogens have generally favorable effects on blood cholesterol and phospholipid concentrations. Estrogens reduce LDL-cholesterol and increase HDL-cholesterol concentrations in a dose-related manner. The decrease in LDL-cholesterol concentrations associated with estrogen therapy appears to result from increased LDL catabolism, while the increase in triglyceride concentrations is caused by increased production of large, triglyceride-rich, very-low-density lipoproteins (VLDLs); changes in serum HDL-cholesterol concentrations appear to result principally from an increase in the cholesterol and apolipoprotein A-1 content of HDL2- and a slight increase in HDL3-cholesterol. /Estrogen General Statement/
For more Mechanism of Action (Complete) data for MESTRANOL (7 total), please visit the HSDB record page.

C21H26O2

310.43

310.193

72-33-3

Mestranol-d2;Mestranol-d4

6291

White to off-white solid powder

1.2±0.1 g/cm3

442.3±45.0 °C at 760 mmHg

153-155 °C(lit.)

190.8±23.0 °C

0.0±1.1 mmHg at 25°C

1.591

5.17

29.46

1

2

2

23

519

5

C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=C3C=CC(=C4)OC

IMSSROKUHAOUJS-UHFFFAOYSA-N

InChI=1S/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3

17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol

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: ≥ 2.08 mg/mL (6.70 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100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，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 2 中的溶解度: ≥ 2.08 mg/mL (6.70 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (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 储备液添加到 900 μL 玉米油中并混合均匀。

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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；
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