E1 Estrogen (Estrone)

Estrone (E1), also known as oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of the three main endogenous estrogens, alongside estradiol and estriol. Estrone and other estrogens are synthesized from cholesterol and primarily secreted by the gonads, though they can also be produced from adrenal androgens in adipose tissue.

Compared to estradiol, estrone and estriol are significantly less potent as estrogens. Estrone can be converted into estradiol, acting mainly as a precursor or metabolic intermediate of estradiol. It serves as both a precursor and metabolite of estradiol.

Besides its role as a natural hormone, estrone has been utilized as a medication, such as in menopausal hormone therapy. For more information on estrone as a medication, refer to the estrone (medication) article.

Biological activity

Estrone is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ. It is considerably less potent than estradiol, making it a relatively weak estrogen. When administered by subcutaneous injection in mice, estradiol is about ten times more potent than estrone and roughly a hundred times more potent than estriol. A study reported that the relative binding affinities of estrone for the human ERα and ERβ were 4.0% and 3.5% of those of estradiol, respectively, and the relative transactivational capacities of estrone at the ERα and ERβ were 2.6% and 4.3% of those of estradiol, respectively.

Consequently, the estrogenic activity of estrone is approximately 4% of that of estradiol. Unlike estradiol and estriol, estrone does not accumulate in estrogen target tissues. Since estrone can be transformed into estradiol, most or all of its estrogenic potency in vivo is due to conversion into estradiol. Thus, estrone is considered a precursor or prohormone of estradiol. Unlike estradiol and estriol, estrone is not a ligand of the G protein-coupled estrogen receptor (affinity >10,000 nM).

With oral administration of estradiol, the ratio of estradiol to estrone levels is about five times higher on average than under normal physiological conditions in premenopausal women and with parenteral (non-oral) routes of estradiol. Oral administration of menopausal replacement doses of estradiol results in low, follicular phase levels of estradiol, while estrone levels resemble the high levels seen during the first trimester of pregnancy.

Despite significantly elevated estrone levels with oral estradiol but not with transdermal estradiol, studies have shown that oral and transdermal estradiol dosages achieving similar estradiol levels have equivalent potency in terms of suppressing luteinizing hormone and follicle-stimulating hormone levels, inhibiting bone resorption, and alleviating menopausal symptoms such as hot flashes.

Additionally, estradiol levels were found to correlate with these effects, whereas estrone levels did not. These findings confirm estrone's very low estrogenic activity and indicate that estrone does not reduce the estrogenic activity of estradiol. This contradicts some cell-free in-vitro research suggesting that high concentrations of estrone might partially antagonize estradiol's actions.

Biosynthesis

Estrone is biosynthesized from cholesterol. The main pathway involves androstenedione as an intermediate, with androstenedione being transformed into estrone by the enzyme aromatase. This reaction occurs in both the gonads and certain other tissues, particularly adipose tissue, and estrone is subsequently secreted from these tissues. Besides the aromatization of androstenedione, estrone is also formed reversibly from estradiol by the enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) in various tissues, including the liver, uterus, and mammary gland.

Mechanism of Action:

Estrone functions by entering cells of certain tissues and binding to nuclear receptors. This interaction influences gene expression, leading to various physiological responses in the body.

Distribution

Estrone is bound approximately 16% to sex hormone-binding globulin (SHBG) and 80% to albumin in the circulation, with the rest (2.0 to 4.0%) circulating freely or unbound. It has about 24% of estradiol's relative binding affinity for SHBG, making estrone relatively poorly bound to SHBG.

Metabolism

Estrone is conjugated into estrogen conjugates such as estrone sulfate and estrone glucuronide by sulfotransferases and glucuronidases, and can also be hydroxylated by cytochrome P450 enzymes into catechol estrogens like 2-hydroxyestrone and 4-hydroxyestrone or into estriol. These transformations occur mainly in the liver. Estrone can also be reversibly converted into estradiol by 17β-HSD. The blood half-life of estrone is about 10 to 70 minutes, similar to that of estradiol.

Estrone, also known as estra-1,3,5(10)-trien-3-ol-17-one, is a naturally occurring estrane steroid with double bonds at the C1, C3, and C5 positions, a hydroxyl group at the C3 position, and a ketone group at the C17 position. The name estrone comes from the chemical terms estrin (estra-1,3,5(10)-triene) and ketone.

The chemical formula of estrone is C18H22O2, and its molecular weight is 270.366 g/mol. It is a white, odorless, solid crystalline powder, with a melting point of 254.5 °C (490 °F) and a specific gravity of 1.23. Estrone is combustible at high temperatures, producing carbon monoxide (CO) and carbon dioxide (CO2).

Chemistry

Estrone, also known as estra-1,3,5(10)-trien-3-ol-17-one, is a naturally occurring estrane steroid with double bonds at the C1, C3, and C5 positions, a hydroxyl group at the C3 position, and a ketone group at the C17 position. The name estrone derives from the chemical terms estrin (estra-1,3,5(10)-triene) and ketone.

Availability of Estrone Medication

Forms of Estrone

Oral Tablets: Available in various dosages.
Transdermal Patches: Applied to the skin for continuous hormone delivery.
Topical Gels or Creams: Applied directly to the skin.
Injectable Forms: Administered via injection, typically for specific medical conditions.

Considerations

Consult with a healthcare professional before starting estrone.
Discuss potential side effects and contraindications.
Regular monitoring may be necessary during treatment.