Estrone

Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Relative to estradiol, both estrone and estriol have far weaker activity as estrogens. It is a far less potent estrogen than is estradiol, and as such, is a relatively weak estrogen. Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol. According to one study, the relative binding affinities of estrone for the human ERα and ERβ were 4.0% and 3.5% of those 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. As such, estrone is considered to be a precursor or prohormone of estradiol. In contrast to estradiol and estriol, estrone is not a ligand of the G protein-coupled estrogen receptor (affinity >10,000 nM).

Clinical research has confirmed the nature of estrone as a relatively inert precursor of estradiol. With oral administration of estradiol, the ratio of estradiol levels to estrone levels is about 5 times higher on average than under normal physiological circumstances in premenopausal women and with parenteral (non-oral) routes of estradiol. In spite of markedly elevated levels of estrone with oral estradiol but not with transdermal estradiol, clinical studies have shown that dosages of oral and transdermal estradiol achieving similar levels of estradiol possess equivalent and non-significantly different potency in terms of measures including suppression of luteinizing hormone and follicle-stimulating hormone levels, inhibition of bone resorption, and relief of menopausal symptoms such as hot flashes. In addition, estradiol levels were found to correlate with these effects, while estrone levels did not.

Biochemistry

thumb|450px|right|class=skin-invert-image|Comprehensive overview of [[steroidogenesis, showing estrone on the lower right among the estrogens.]]

Biosynthesis

Estrone is biosynthesized from cholesterol. The principal pathway involves androstenedione as an intermediate, with androstenedione being transformed into estrone by the enzyme aromatase. This reaction occurs in both the gonads and in certain other tissues, particularly adipose tissue, and estrone is subsequently secreted from these tissues.

Distribution

Estrone is bound approximately 16% to sex hormone-binding globulin (SHBG) and 80% to albumin in the circulation, It has about 24% of the relative binding affinity of estradiol for 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 such as 2-hydroxyestrone and 4-hydroxyestrone or into estriol.

Excretion

Estrone is excreted in urine in the form of estrogen conjugates such as estrone sulfate.

Levels

<big>Toxicity:</big>

When estrone is used too much or taken in large amounts, it can cause toxicity, leading to symptoms like nausea and vomiting. Estrone should be stored in its original package or container to maintain its quality and effectiveness. Estrone is combustible at high temperatures, with the products carbon monoxide (CO) and carbon dioxide (CO₂).

Medical use

Estrone has been available as an injected estrogen for medical use, for instance in hormone therapy for menopausal symptoms, but it is now mostly no longer marketed.

Estrone, as part of hormone replacement therapy (HRT), is frequently used to treat symptoms caused by estrogen deficiency in peri and post-menopausal women. This therapy aims to enhance overall health and relieve menopausal symptoms related to estrogen imbalance. Additionally, estrone and other estrogens are used to prevent osteoporosis in postmenopausal women who are at high risk of fractures and cannot tolerate alternative medications. Estrogens are absorbed efficiently by the body and subsequently inactivated in the liver, making them effective in HRT and osteoporosis prevention. Those with breast cancer become at a greater risk of hypercalcemia and bone metastases when taking estrogens. Post-menopausal women with breast cancer can be seen to develop frailty syndrome when there are changes in blood hormonal levels, including an increased level of estrone. Estrone, the major type of estrogen produced in post-menopausal women, was seen in greater concentrations from standard levels in those that were categorized as prefrail and in those that classified as frail.

Venous Thromboembolism

The risk of VTE is increased in those that use estrogens, those that currently have or have a history with VTE are at a greater risk of reoccurring VTE with the usage of estrogens. The use of estrogens within three weeks postpartum may increase the risk of developing a VTE. Risk of developing initial VTE is also increased with familial history, genetic mutations: factor V Leiden and prothrombin-G20210A, and pregnancy-postpartum with the use of estrogens.

Breastfeeding

The use of estrogens may affect the ability to breastfeed and can change the composition of breastmilk. Estrogens have been used to suppress lactation which can result in a reduced total duration of lactation and reduced volume or inability to produce breastmilk. Composition of breastmilk produced was also seen to be different resulting in a reduced concentration of proteins in the milk. Babies of mothers that were taking estrogens while breastfeeding were seen to experience slower weight gain.

Adverse effect

Some adverse effects seen with the usage of estrogens include: increased risk of venous thromboembolism (VTE), stroke, breast cancer, hypertension, and vaginitis.

History

Estrone was the first steroid hormone to be discovered. It was discovered in 1929 independently by the American scientists Edward Doisy and Edgar Allen and the German biochemist Adolf Butenandt, although Doisy and Allen isolated it two months before Butenandt. They isolated and purified estrone in crystalline form from the urine of pregnant women. Doisy and Allen named it theelin, while Butenandt named it progynon and subsequently referred to it as folliculin in his second publication on the substance. Butenandt was later awarded the Nobel Prize in 1939 for the isolation of estrone and his work on sex hormones in general. The molecular formula of estrone was known by 1931, and its chemical structure had been determined by Butenandt by 1932. and the name estrone, on the basis of its C17 ketone group, was formally established in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London.

A partial synthesis of estrone from ergosterol was accomplished by Russell Earl Marker in 1936, and was the first chemical synthesis of estrone. An alternative partial synthesis of estrone from cholesterol by way of dehydroepiandrosterone (DHEA) was developed by Hans Herloff Inhoffen and Walter Hohlweg in 1939 or 1940,