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

natural Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are part ...

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

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 estradiol ...

. E2S itself is biologically inactive, but it can be converted by

steroid sulfatase Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a sulfatase enzyme involved in the metabolism of steroids. It is encoded by the ''STS'' gene. Reactions This enzyme catalysis, catalyses the follow ...

(also called estrogen sulfatase) into

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

, which is a potent

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

. Simultaneously, estrogen sulfotransferases convert estradiol to E2S, resulting in an

equilibrium Equilibrium may refer to: Film and television * ''Equilibrium'' (film), a 2002 science fiction film * '' The Story of Three Loves'', also known as ''Equilibrium'', a 1953 romantic anthology film * "Equilibrium" (''seaQuest 2032'') * ''Equilibr ...

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 men ...

(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 breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

tissue, and E2S has been implicated in the biology of

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

via serving as an active reservoir of estradiol. As the

sodium salt Sodium salts are salt (chemistry), salts composed of a sodium cation and any anion. The anion may be the conjugate base of some Inorganic compound, inorganic or organic acids, or any monatomic or polyatomic anion. They can be formed by the Neutra ...

sodium estradiol sulfate, E2S is present as a minor constituent (0.9%) of

conjugated equine estrogen 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 th ...

s (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 th ...

. It effectively functions as a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

to estradiol in this preparation, similarly to E1S. E2S is also formed as a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of estradiol, as well as of estrone and E1S. Aside from its presence in CEEs, E2S is not available as a commercial

pharmaceutical drug Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, 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 ...

. 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 ho ...

in activating the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

s relative to estradiol ''

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

''. It is 10-fold less potent than

orally 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, an ...

uterotrophic The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

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

estrogenic Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three maj ...

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 th ...

(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 Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

glutathione S-transferase Glutathione ''S''-transferases (GSTs), previously known as ligandins, are a family of eukaryote, eukaryotic and prokaryote, prokaryotic Biotransformation#Phase II reaction, phase II metabolic isozymes best known for their ability to Catalysis, ...

, an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It 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 ...

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 an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

in 89% of cycles (47 of 53).

References

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

See also

References