Estrone (formerly known as E1, and oestrone) is an endogenous estrogenic hormone and a minor female sex hormone secreted by the ovary as well as adipose tissue. Estrone is a weak estrogen and is one of the three natural estrogens, with the other two being estriol and estradiol. Estrone is the least abundant of the three hormones; estradiol is present almost always in the reproductive female body, and estriol is abundant primarily during pregnancy. Estrone is relevant to health and disease states because of its conversion to estrone sulfate, a long-lived derivative.

Physicochemical Properties

Molecular Formula	C18H22O2
Molecular Weight	270.37
Exact Mass	270.161
CAS #	53-16-7
Related CAS #	53-16-7
PubChem CID	5870
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	445.2±45.0 °C at 760 mmHg
Melting Point	258-260 °C(lit.)
Flash Point	189.7±21.3 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.587
LogP	3.69
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Heavy Atom Count	20
Complexity	418
Defined Atom Stereocenter Count	4
SMILES	C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=C3C=CC(=C4)O
InChi Key	DNXHEGUUPJUMQT-CBZIJGRNSA-N
InChi Code	InChI=1S/C18H22O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-16,19H,2,4,6-9H2,1H3/t14-,15-,16+,18+/m1/s1
Chemical Name	(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one
Synonyms	Oestrone; E1
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo	Objectives: To gain further data on the hormonal control of pregnancy in the donkey and to obtain reference values for hormonal pregnancy testing. Material and methods: Blood samples were collected at monthly intervals from 23 donkey mares with normal singleton pregnancies. Further samples were obtained from six mares displaying pregnancies with clinical disorders. Progesterone (P4), total estrone (TE), free (E) and conjugated estrone (ES) were determined using radioimmunoassay. Results: Mean duration of pregnancy was 372 ± 16 days. It was longer (p < 0.05) in large (375.9 ± 5.7 days) and standard (385.8 ± 20.7 days) donkeys than in miniature donkeys (357.4 ± 5.7 days) and negatively correlated to the age of the mare (p = 0.043). P4-concentrations varied between 12-35 ng/ml during weeks 2-5 of pregnancy and increased thereafter in eight jennies concomitant with the formation of the secondary corpora lutea (sCL), reaching values of 40-110 ng/ml during weeks 12-17. The decrease observed thereafter resulted in concentrations between 5-16 ng/ml until week 46, followed by a slight increase in most of the mares prior to parturition. Concentrations of TE remained < 1 ng/ml until week 6. They increased thereafter to 600-2700 ng/ml during midpregnancy and displayed a decrease to 1-20 ng/ml during the last 2 weeks of pregnancy. The course of E and ES was correlated (p < 0.0001) and E concentrations were up to 1000 times lower than those of ES. The course of hormone concentrations did not provide any clear indications in relation to the observed clinical disorders. Conclusion: The course of P4-concentrations resembles largely the situation in the horse. In contrast to the horse, the course of ES does not show an increase concomitant with the formation of the sCL. Breed-specific effects became apparent regarding pregnancy duration.[2]
ADME/Pharmacokinetics	Absorption, Distribution and Excretion 43% The natural estrogens are generally quickly and well absorbed from the gastrointestinal tract, there being little difference between estrone, estradiol and estriol. Estrogens are inactivated in the liver. A proportion of absorbed estrogen is excreted in the bile and then reabsorbed from the intestine. The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin. Following administration of Hormonin, physiological estrogen concentrations are achieved at different rates. The maximum plasma levels and the time to reach the peak in the plasma level varied between subjects and was; estrone 750-2116 pmol/litre, 0.5-6.0 hours; estradiol 246-813 pmol/litre, 1-8 hours; estriol 173-241 pmol/litre, 5-12 hours. Following steady state conditions after cessation of Hormonin therapy, estrogen levels remained in the pre-menopausal range for approximately 48 hours. Estrogens are available for oral, parenteral, transdermal, or topical administration ... absorption is generally good with the appropriate preparation. /Estrogens/ For more Absorption, Distribution and Excretion (Complete) data for ESTRONE (11 total), please visit the HSDB record page. Metabolism / Metabolites Hepatic. 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. In the liver estradiol is readily oxidised to estrone and both estradiol and estrone are converted by hydration to estriol. Metabolites of estrogens are mainly excreted in the urine as conjugates of glucuronic and sulphuric acid. The 17beta-hydroxy steroid dehydrogenase transforms estrone to estradiol reversibly. This enzyme occurred in all tissues of all species examined and is linked to either the cytosolic or microsomal subcellular compartment. In human liver, a NAD-linked 17beta-hydroxy steroid 3-hydrogenase occurs in cytosol and in microsomes, and a further NADP-linked enzyme has been found in cytosol. Hence, estrone and estradiol are largely biologically equivalent; they are also metabolized via the same pathways. The steroidal estrogens are metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The steroids and their metabolites are conjugated at the hydroxyl group of the C 3 position with sulfuric or glucuronic acid; these conjugates may undergo further metabolic change. Conjugation increases water solubility and facilitates excretion in urine. Large amounts of free estrogens are also distributed into the bile, reabsorbed from the GI tract, and recirculated through the liver where further degradation occurs. /Estrogen General Statement/ For more Metabolism/Metabolites (Complete) data for ESTRONE (13 total), please visit the HSDB record page. Estrone has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl]oxy]oxane-2-carboxylic acid. Hepatic. Half Life: 19 hours Biological Half-Life 19 hours
Toxicity/Toxicokinetics	Toxicity Summary Estrogens enter the cells of responsive tissues (e.g. female organs, breasts, hypothalamus, pituitary) where they interact with estrogen receptors. Hormone-bound estrogen receptors dimerize, translocate to the nucleus of cells and bind to estrogen response elements (ERE) of genes. Binding to ERE alters the transcription rate of affected genes. 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) release from the anterior pituitary. Protein Binding > 95% Interactions Within the framework of experiments related to the association between dietary fiber and breast cancer an in vitro test system was used to study the binding of estrogens to various fibers (eg cholestyramin, lignin and cellulose) and fiber sources (eg wheat bran, cereals, seeds and legumes). Furthermore, the in vivo apparent digestibility of the different fiber sources was tested using a mobile nylon bag technique in intestine-cannulate pigs. Estradiol-(17) beta bound more strongly to the various fibers than did estrone, estriol or estrone-3-glucuronide. At increasing pH (greater than 7) binding of both estrone and estradiol-(17) beta to wheat bran decreased significantly. Cholestyramine and lignin bound almost all estrogens present in the medium. Linseed (91%), oats (83%), barley chaff (88%) and wheat bran (82%) are other excellent binders of estradiol-(17) beta. Corn rye and white wheat flour showed lower binding capacity with a relatively low affinity. Cereals with the highest percentage of lignin in the fiber (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens bound with the highest affinity (relative to bovine serum albumin) to these fiber sources. Together with wheat bran and lignin, oats, linseed and soybean seem to be products with good perspectives for in vivo evaluation of the lowering effect of dietary fiber on estrogen exposure of estrogen sensitive tissues. Estrogens may interfere with the effects of bromocriptine; dosage adjustment may be necessary. /Estrogens/ 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 ESTRONE (14 total), please visit the HSDB record page.
References	Endocrinology.1952 Sep;51(3):173-82;Tierarztl Prax Ausg G Grosstiere Nutztiere.2014;42(1):32-9..
Additional Infomation	Therapeutic Uses Estrogens Esterified Estrogens and Methyltestosterone Tablets H.S. and Esterified Estrogens and Methyltestosterone Tablets D.S. are indicated in the: Treatment of moderate to severe vasomotor symptoms associated with the menopause in those patients not improved by estrogens alone. (There is no evidence that estrogens are effective for nervous symptoms or depression without associated vasomotor symptoms, and they should not be used to treat such conditions.) /Included in US product label/ /Estrone is indicated as/ Hormone replacement therapy (HRT) for estrogen deficiency symptoms in peri- and post-menopausal women. Prevention of osteoporosis in post-menopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis. Esterified estrogens /is indicated/ for replacement in female hypogonadism... For more Therapeutic Uses (Complete) data for ESTRONE (9 total), please visit the HSDB record page. 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 or dementia. The estrogen alone substudy of the Women's Health Initiative (WHI) reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with oral conjugated estrogens (CE 0.625 mg) alone per day, 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. Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. For more Drug Warnings (Complete) data for ESTRONE (45 total), please visit the HSDB record page. Pharmacodynamics Estrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency.

Solubility Data

Solubility (In Vitro)

DMSO:54 mg/mL (199.7 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6986 mL	18.4932 mL	36.9864 mL
	5 mM	0.7397 mL	3.6986 mL	7.3973 mL
	10 mM	0.3699 mL	1.8493 mL	3.6986 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.