Estradiol sulfate (E2S), or 17β-estradiol 3-sulfate, is a

natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...

, endogenous steroid and an

estrogen ester An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradio ...

. E2S itself is biologically inactive, but it can be converted by steroid sulfatase (also called estrogen sulfatase) into

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

, which is a potent

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

. Simultaneously, estrogen sulfotransferases convert estradiol to E2S, resulting in an equilibrium between the two steroids in various tissues.

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. Estrone, as well as the other estrogens, are synthesized ...

and E2S are the two immediate metabolic sources of estradiol. E2S can also be metabolized into

estrone sulfate Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate. In addition to its role as a natural hormone, estrone sulfate is used as a medication, for instance in menop ...

(E1S), which in turn can be converted into estrone and estradiol. Circulating concentrations of E2S are much lower than those of E1S. High concentrations of E2S are present in

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and sec ...

tissue, and E2S has been implicated in the biology of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

via serving as an active reservoir of estradiol. As the

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

, sodium estradiol sulfate, E2S is present as a minor constituent (0.9%) of conjugated equine estrogens (CEEs), or

Premarin Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the ...

. It effectively functions as a prodrug to estradiol in this preparation, similarly to E1S. E2S is also formed as a metabolite of estradiol, as well as of estrone and E1S. Aside from its presence in CEEs, E2S is not available as a commercial

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field an ...

. E2S shows about 10,000-fold lower

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

in activating the

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

s relative to estradiol ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

''. It is 10-fold less potent than

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

ly in terms of ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

uterotrophic The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ut ...

effect in rats. Estrogen sulfates like estradiol sulfate or estrone sulfate are about twice as potent as the corresponding free estrogens in terms of

ic effect when given orally to rodents. This in part led to the introduction of

conjugated estrogens Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the ...

(Premarin), which are primarily estrone sulfate, in 1941. Although inactive at

steroid hormone receptor Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...

s, E2S has been found to act as a potent inhibitor of

glutathione S-transferase Glutathione ''S''-transferases (GSTs), previously known as ligandins, are a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) ...

, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that contributes to the inactivation of estradiol via conversion of it into an estradiol-

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...

conjugate. As such, E2S can indirectly serve as a positive effector of estrogen signaling. Estradiol levels are about 1.5- to 4-fold higher than E2S levels in women. This is in contrast to E1S, the levels of which are about 10 to 15 times higher than those of estrone. E2S at an oral dosage of 5 mg/day in women resulted in inhibition of

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...

in 89% of cycles (47 of 53).

References

{{Estrogen receptor modulators Estradiol esters Human metabolites Phenol esters Sulfate esters

See also

References