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]

Absorption, Distribution and Excretion
43%
Natural estrogens are generally rapidly and fully absorbed by the gastrointestinal tract, with little difference in absorption among estrone, estradiol, and estriol. Estrogens are inactivated in the liver. A portion of absorbed estrogens is excreted via bile and then reabsorbed by the intestines.
The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed throughout the body, typically reaching higher concentrations in sex hormone target organs. Estrogens primarily bind to sex hormone-binding globulin (SHBG) and albumin, circulating in the bloodstream.
The rate at which physiological estrogen concentrations are reached after taking Hormonin varies from person to person. Peak plasma concentrations and the time to reach peak concentrations vary; estrone 750-2116 pmol/L, 0.5-6.0 hours; estradiol 246-813 pmol/L, 1-8 hours; estriol 173-241 pmol/L, 5-12 hours. After cessation of hormone therapy, estrogen levels remain within the premenopausal range for approximately 48 hours after reaching steady state. Estrogens can be administered orally, by injection, transdermally, or topically…with appropriate formulations, absorption is generally good. /Estrogens/ For more complete data on the absorption, distribution, and excretion of estrone (11 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism. Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens are in a dynamic equilibrium of metabolic interconversions. These conversions primarily occur in the liver. Estradiol is reversibly converted to estrone, and both can be converted to estriol, the main urinary metabolite. Estrogens also undergo enterohepatic circulation via sulfate and glucuronide conjugation in the liver. The conjugates are secreted into the intestine via bile and are hydrolyzed and reabsorbed in the intestine. In postmenopausal women, a significant portion of circulating estrogens exists as sulfate conjugates, particularly estrone sulfate, which serves as a circulating reservoir for the synthesis of more active estrogens. In the liver, estradiol is readily oxidized to estrone, and both estradiol and estrone can be converted to estriol via hydration. Estrogen metabolites are primarily excreted in urine as glucuronic acid and sulfate conjugates. 17β-hydroxysteroid dehydrogenase reversibly converts estrone to estradiol. This enzyme is present in all tissues of all tested species and is associated with subcellular compartments in the cytoplasm or microsomes. In the human liver, NAD-dependent 17β-hydroxysteroid 3-hydrogenases are present in both the cytoplasm and microsomes, and another NADP-dependent enzyme has also been found in the cytoplasm. Therefore, estrone and estradiol are largely biologically equivalent; their metabolic pathways are also identical. Steroid estrogens are primarily metabolized in the liver, but the kidneys, gonads, and muscle tissue may also be involved to some extent. Steroids and their metabolites bind to sulfate or glucuronic acid at the C3 hydroxyl group; these conjugates may undergo further metabolic changes. This binding increases water solubility and promotes urinary excretion. A significant amount of free estrogen is also distributed in the bile, reabsorbed from the gastrointestinal tract, and re-enters the hepatic circulation, where it is further degraded. /Estrogen Overview/
For more complete data on the metabolism/metabolites of estrone (13 metabolites in total), please visit the HSDB record page.
Known human metabolites of estrone 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]phenanthrene-3-yl]oxy]oxacyclohexane-2-carboxylic acid.
Primarily metabolized in the liver.
Half-life: 19 hours

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Biological half-life
19 hours

Toxicity Summary
Estrogen enters cells of reactive tissues (e.g., female organs, breast, hypothalamus, pituitary gland) and interacts with estrogen receptors. Estrogen-binding estrogen receptors dimerize, translocate to the cell nucleus, and bind to estrogen response elements (EREs) in genes. Binding to EREs alters the transcription rate of affected genes. Estrogen increases the production of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins in the liver and inhibits the release of follicle-stimulating hormone (FSH) from the anterior pituitary. Protein Binding 95% Interaction Within the framework of studies on the association between dietary fiber and breast cancer, we investigated the binding of estrogen to various fibers (e.g., cholestyramine, lignin, and cellulose) and fiber sources (e.g., wheat bran, cereals, seeds, and legumes) using in vitro assay systems. Furthermore, we tested the apparent in vivo digestibility of different fiber sources using a mobile nylon bag technique in intestinal-tubed pigs. The results showed that estradiol-(17)β had a stronger binding affinity to various fibers than estrone, estriol, or estrone-3-glucuronide. The binding affinity of both estrone and β-estradiol to wheat bran was significantly reduced at elevated pH (greater than 7). Cholestyramine and lignin could bind almost all estrogens present in the culture medium. Flaxseed (91%), oats (83%), barley bran (88%), and wheat bran (82%) were also excellent binders of β-estradiol. Corn, rye, and white wheat flour showed lower binding affinity and relatively lower affinity. The cereals with the highest lignin content (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens showed the highest affinity for these fiber sources (relative to bovine serum albumin). Along with wheat bran and lignin, oats, flaxseed, and soybean appear to be promising products for in vivo evaluation of the effects of dietary fiber on reducing estrogen exposure in estrogen-sensitive tissues.
Estrogens may interfere with the action of bromocriptine; dosage adjustments may be necessary. /Estrogen/
Concomitant use with estrogen may increase calcium absorption and worsen kidney stones in susceptible individuals; this can be used as a therapeutic advantage to increase bone mass. /Estrogen/
Concomitant use of /glucocorticoid steroids/ with estrogen may alter glucocorticoid metabolism and protein binding, leading to decreased clearance, prolonged elimination half-life, and enhanced therapeutic and toxic effects of glucocorticoids; dosage adjustments of glucocorticoids may be necessary during and after concomitant use. /Estrogen/
For more complete data on interactions of ESTRONE (14 in total), please visit the HSDB records page.

Endocrinology.1952 Sep;51(3):173-82;Tierarztl Prax Ausg G Grosstiere Nutztiere.2014;42(1):32-9..

Therapeutic Uses

Estrogen
Esterified Estrogen and Methyltestosterone Tablets HS and esterified estrogen and methyltestosterone Tablets DS are indicated for: the treatment of menopausal-related moderate to severe vasomotor symptoms that are unresponsive to estrogen monotherapy. (There is no evidence that estrogen is effective for neurological symptoms or depression without vasomotor symptoms, and therefore it should not be used to treat such conditions.) /US product label contains/
/Estrogen is indicated for/ Hormone replacement therapy (HRT) for symptoms of estrogen deficiency in perimenopausal and postmenopausal women. For the prevention of osteoporosis in postmenopausal women at high risk of fracture who cannot tolerate or are contraindicated for other approved medications for the prevention of osteoporosis.
Esterified estrogen is indicated for the replacement therapy of female hypogonadism…
For more complete data on the therapeutic uses of estrogen (9 types), please visit the HSDB record page.
Drug Warnings

Estrogen increases the risk of endometrial cancer: Close monitoring of all women taking estrogen is essential. For all cases of undiagnosed persistent or recurrent abnormal vaginal bleeding, adequate diagnostic measures should be taken, including endometrial sampling if necessary to rule out malignancy. There is no evidence that the use of “natural” estrogen results in a different endometrial risk compared to the use of an equivalent dose of synthetic estrogen.
Cardiovascular and other risks: Estrogen (whether or not used in combination with progesterone) should not be used to prevent cardiovascular disease or dementia. A sub-study of the Women’s Health Initiative (WHI) using estrogen alone reported that postmenopausal women (50 to 79 years of age) had an increased risk of stroke and deep vein thrombosis (DVT) after 6.8 and 7.1 years of daily oral conjugated estrogen (CE 0.625 mg), respectively, compared to the placebo group.
The Women’s Health Initiative Memory Study (WHIMS), a sub-study of WHI, reported that postmenopausal women aged 65 years and older had an increased risk of developing possible dementia after 4 years of treatment with oral conjugated estrogen in combination with medroxyprogesterone acetate, compared to the placebo group. It is unclear whether this finding applies to younger postmenopausal women or women receiving estrogen therapy alone. The WHI clinical trials did not investigate other doses of oral conjugated estrogen with medroxyprogesterone acetate, or other combinations and formulations of estrogen and progestin. Due to the lack of comparable data, these risks should be assumed to be similar. Given these risks, estrogen (whether or not in combination with progestin) should be prescribed at the lowest effective dose and for the shortest duration, based on treatment goals and the individual woman's risk. Given these risks, regardless of whether progestin is combined, the prescribed dose of estrogen should be as low as possible, the duration as short as possible, and should be consistent with treatment goals and the individual woman's risk.
For more complete data on drug warnings for estrone (45 in total), please visit the HSDB record page.

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Pharmacodynamics
Estrone is a synthetic or naturally occurring steroidal estrogen extracted from the urine of pregnant horses and is the primary circulating estrogen in postmenopausal women. Estrone is naturally derived from aromatase in adipose tissue, which converts androstenedione to estradiol, and further to estradiol in peripheral tissues. Estrone has approximately one-third the estrogenic potency of estradiol. Estrone sulfate is piperazine-stabilized estrone sulfate. Estrone and estradiol are used to treat abnormalities associated with gonadotropin dysfunction, vasomotor symptoms, atrophic vaginitis, and menopausal vulvar atrophy, as well as to prevent osteoporosis caused by estrogen deficiency.

C18H22O2

270.37

270.161

53-16-7

5870

White to off-white solid powder

1.2±0.1 g/cm3

445.2±45.0 °C at 760 mmHg

258-260 °C(lit.)

189.7±21.3 °C

0.0±1.1 mmHg at 25°C

1.587

3.69

1

2

0

20

418

4

C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=C3C=CC(=C4)O

DNXHEGUUPJUMQT-CBZIJGRNSA-N

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

(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one

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)

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)