Reaction Process: WikiPathways:WP5276
Estrogen metabolism related metabolites
find 16 related metabolites which is associated with chemical reaction(pathway) Estrogen metabolism
2-Methoxyestradiol ⟶ 2-methoxy-17beta-estradiol 3-glucuronide
2-Methoxyestradiol
2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It is derived from estrogen, although it binds poorly to known estrogen receptors, and belongs to the family of drugs called angiogenesis inhibitors. It has undergone Phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. The CAS name for 2ME2 is (17 beta)-2-methoxyestra-1,3,5(10)-triene-3,17-diol. It also acts as a vasodilator. [HMDB] 2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumours need in order to grow (angiogenesis). It is derived from estrogen, although it binds poorly to known estrogen receptors, and belongs to the family of drugs called angiogenesis inhibitors. It has undergone phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. 2ME2 also acts as a vasodilator. C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C1821 - Selective Estrogen Receptor Modulator C274 - Antineoplastic Agent > C129818 - Antineoplastic Hormonal/Endocrine Agent > C481 - Antiestrogen C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D050258 - Mitosis Modulators > D050256 - Antimitotic Agents > D050257 - Tubulin Modulators D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones D000970 - Antineoplastic Agents > D050256 - Antimitotic Agents C147908 - Hormone Therapy Agent > C547 - Hormone Antagonist C1892 - Chemopreventive Agent 2-Methoxyestradiol (2-ME2), an orally active endogenous metabolite of 17β-estradiol (E2), is an apoptosis inducer and an angiogenesis inhibitor with potent antineoplastic activity. 2-Methoxyestradiol also destablize microtubules. 2-Methoxyestradio, also a potent superoxide dismutase (SOD) inhibitor and a ROS-generating agent, induces autophagy in the transformed cell line HEK293 and the cancer cell lines U87 and HeLa[1][2][3][4][5][6].
2-Methoxyestrone
2-Methoxyestrone (or 2-ME1) belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Thus, 2-methoxyestrone is considered to be a steroid or steroid derivative. It is a by-product of estrone and 2-hydroxyestrone metabolism and has been detected in all mammals. More specifically, 2-methoxyestrone is an endogenous, naturally occurring methoxylated catechol estrogen and a metabolite of estrone that is formed by catechol O-methyltransferase via the intermediate 2-hydroxyestrone. 2-Methoxyestrone is part of the androgen and estrogen metabolic pathway. The acid ionization constant (pKa) of 2-methoxyestrone has been determined to be 10.81 (PMID: 516114). 2-Methoxyestrone can be metabolized to a sulfated derivative (2-methoxyestrone 3-sulfate) via steroid sulfotransferase (EC 2.8.2.15). It can also be glucuronidated to 2-methoxyestrone 3-glucuronide by UDP glucuronosyltransferase (EC 2.4.1.17). Unlike estrone but similarly to 2-hydroxyestrone and 2-methoxyestradiol, 2-methoxyestrone has very low affinity for the estrogen receptor and lacks significant estrogenic activity (PMID: 10865186). 2-methoxyestrone is a steroid derivative that is a byproduct of estrone and 2-hydroxyestrone metabolism. It is part of the androgen and estrogen metabolic pathway. The acid ionization constant (pKa) of 2-methoxyestrone is 10.81 (PMID: 516114). 2-Methoxyestrone can be metabolized to a sulfated derivative (2-Methoxyestrone 3-sulfate) via steroid sulfotransferase (EC 2.8.2.15). It can also be glucuronidated to 2-Methoxyestrone 3-glucuronide by UDP glucuronosyltransferase (EC 2.4.1.17). [HMDB] C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones 2-Methoxyestrone is a methoxylated catechol estrogen and metabolite of estrone, with a pKa of 10.81.
Androstenedione
Androst-4-en-3,17-dione, also known as androstenedione or delta(4)-androsten-3,17-dione, belongs to androgens and derivatives class of compounds. Those are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans. Thus, androst-4-en-3,17-dione is considered to be a steroid lipid molecule. Androst-4-en-3,17-dione is practically insoluble (in water) and an extremely weak acidic compound (based on its pKa). Androst-4-en-3,17-dione can be found in a number of food items such as naranjilla, purslane, common cabbage, and oval-leaf huckleberry, which makes androst-4-en-3,17-dione a potential biomarker for the consumption of these food products. Androst-4-en-3,17-dione can be found primarily in blood, cerebrospinal fluid (CSF), and urine, as well as throughout most human tissues. In humans, androst-4-en-3,17-dione is involved in a couple of metabolic pathways, which include androgen and estrogen metabolism and androstenedione metabolism. Androst-4-en-3,17-dione is also involved in a couple of metabolic disorders, which include 17-beta hydroxysteroid dehydrogenase III deficiency and aromatase deficiency. Moreover, androst-4-en-3,17-dione is found to be associated with rheumatoid arthritis, thyroid cancer , cushings Syndrome, and schizophrenia. Androst-4-en-3,17-dione is a non-carcinogenic (not listed by IARC) potentially toxic compound. Androstenedione is a delta-4 19-carbon steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol. It is the common precursor of male and female sex hormones. Some androstenedione is also secreted into the plasma and may be converted in peripheral tissues to testosterone and estrogens. Androstenedione originates either from the conversion of dehydroepiandrosterone or from 17-hydroxyprogesterone. It is further converted to either testosterone or estrone. The production of adrenal androstenedione is governed by ACTH, while the production of gonadal androstenedione is under control by gonadotropins. CONFIDENCE standard compound; INTERNAL_ID 396; DATASET 20200303_ENTACT_RP_MIX505; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 9081; ORIGINAL_PRECURSOR_SCAN_NO 9076 CONFIDENCE standard compound; INTERNAL_ID 396; DATASET 20200303_ENTACT_RP_MIX505; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 9111; ORIGINAL_PRECURSOR_SCAN_NO 9108 CONFIDENCE standard compound; INTERNAL_ID 396; DATASET 20200303_ENTACT_RP_MIX505; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 9069; ORIGINAL_PRECURSOR_SCAN_NO 9064 CONFIDENCE standard compound; INTERNAL_ID 396; DATASET 20200303_ENTACT_RP_MIX505; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 9077; ORIGINAL_PRECURSOR_SCAN_NO 9075 CONFIDENCE standard compound; INTERNAL_ID 396; DATASET 20200303_ENTACT_RP_MIX505; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 9113; ORIGINAL_PRECURSOR_SCAN_NO 9112 C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones CONFIDENCE standard compound; INTERNAL_ID 2803 INTERNAL_ID 2803; CONFIDENCE standard compound CONFIDENCE standard compound; INTERNAL_ID 4165
16a-Hydroxyestrone
16a-Hydroxyestrone or 16alpha-hydroxyestrone (16α-OH-E1 or 16a OHE1), or hydroxyestrone, is an endogenous steroidal estrogen and a major metabolite of estrone and estradiol. 16a-hydroxyestrone belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Thus, 16a-hydroxyestrone is considered to be a steroid molecule. 16a-hydroxyestrone is found in all vertebrates. Vertebrates, especially mammals, metabolizes estrogen into two major pathways and one minor. The two major pathways lead to 2-hydroxyestrone and 16a-hydroxyestrone (2-OHE1 and 16a OHE1 respectively). The minor pathway leads to 4-hydroxyestrone (4-OHE1). 2a-hydroxyestrone is considered to be the good metabolite (PMID: 8943806) as 2-hydroxyestrone does not stimulate cell growth and it blocks the action of stronger estrogens that may be carcinogenic. 16a-Hydroxyestrone, on the other hand, has a significantly stronger estrogenic activity, and studies show that it may increase the risk of breast cancer. The binding of 16a-hydroxyestrone to the estrogen receptor is reported to be covalent and irreversible (PMID: 3186693). A low urinary ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone is a strong predictor of breast cancer risk among women (PMID: 19502596). Estrone (also oestrone) is an estrogenic hormone secreted by the ovary. Its molecular formula is C18H22O2. estrone has a melting point of 254.5 degrees Celsius. estrone is one of the three estrogens, which also include estriol and estradiol. estrone is the least prevalent of the three hormones, estradiol being prevalent almost always in a female body, estriol being prevalent primarily during pregnancy. estrone sulfate is relevant to health and disease due to its conversion to estrone sulfate, a long-lived derivative of estrone. estrone sulfate acts as a pool of estrone which can be converted as needed to the more active estradiol. [HMDB] C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones
Testosterone
Testosterone is the primary male sex hormone and anabolic steroid from the androstane class of steroids. It is the most important androgen in potency and quantity for vertebrates. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. In addition, testosterone is involved in health and well-being, and the prevention of osteoporosis. Testosterone exerts its action through binding to and activation of the androgen receptor. In mammals, testosterone is metabolized mainly in the liver. Approximately 50\\% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases. An additional 40\\% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5alpha- and 5beta-reductases, 3alpha-hydroxysteroid dehydrogenase, and 17beta-HSD. Like other steroid hormones, testosterone is derived from cholesterol. The first step in the biosynthesis of testosterone involves the oxidative cleavage of the side-chain of cholesterol by the cholesterol side-chain cleavage enzyme (P450scc, CYP11A1) to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A1 (17alpha-hydroxylase/17,20-lyase) enzyme to yield a variety of C19 steroids. In addition, the 3beta-hydroxyl group is oxidized by 3beta-hydroxysteroid dehydrogenase to produce androstenedione. In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17beta-hydroxysteroid hydrogenase to yield testosterone. Testosterone is synthesized and released by the Leydig cells in the testes that lie between the tubules and comprise less than 5\\% of the total testicular volume. Testosterone diffuses into the seminiferous tubules where it is essential for maintaining spermatogenesis. Some testosterone binds to an androgen-binding protein (ABP) that is produced by the Sertoli cells and is homologous to the sex-hormone binding globulin that transports testosterone in the general circulation. The ABP carries testosterone in the testicular fluid where it maintains the activity of the accessory sex glands and may also help to retain testosterone within the tubule and bind excess free hormone. Some testosterone is converted to estradiol by Sertoli cell-derived aromatase enzyme. Leydig cell steroidogenesis is controlled primarily by luteinizing hormone with negative feedback of testosterone on the hypothalamic-pituitary axis. The requirement of spermatogenesis for high local concentrations of testosterone means that loss of androgen production is likely to be accompanied by loss of spermatogenesis. Indeed, if testicular androgen production is inhibited by the administration of exogenous androgens then spermatogenesis ceases. This is the basis of using exogenous testosterone as a male contraceptive. The largest amounts of testosterone (>95\\%) are produced by the testes in men, while the adrenal glands account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, thecal cells of the ovaries, and, during pregnancy, by the placenta. Testosterone levels fall by about 1\\% each year in men. Therefore, with increasing longevity and the aging of the population, the number of older men with testosterone deficiency will increase substantially over the next several decades. Serum testosterone levels decrease progressively in aging men, but the rate and magnitude of decrease vary considerably. Approximately 1\\% of healthy young men have total serum testosterone levels below normal; in contrast, approximately 20\\% of healthy men over age 60 years have serum testosterone levels below normal. (PMID: 17904450, 17875487). G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03B - Androgens > G03BA - 3-oxoandrosten (4) derivatives D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones > D000728 - Androgens C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C2360 - Anabolic Steroid
Estrone
Estrone is a major mammalian estrogen. The conversion of the natural C19 steroids, testosterone and androstenedione into estrone is dependent on a complex key reaction catalyzed by the cytochrome P450 aromatase (EC 1.14.14.1, unspecific monooxygenase), which is expressed in many tissues of the adult human (e.g. ovary, fat tissue), but not in the liver. The ovaries after menopause continue to produce androstenedione and testosterone in significant amounts and these androgens are converted in fat, muscle, and skin into estrone. When women between the ages of 45 and 64 years have prophylactic oophorectomy (when hysterectomy is performed for benign disease to prevent the development of ovarian cancer), evidence suggests that oophorectomy increases the subsequent risk of coronary heart disease (CHD) and osteoporosis. Whereas 14,000 women die of ovarian cancer every year nearly 490,000 women die of heart disease and 48,000 women die within 1 year after hip fracture. Therefore, the decision to perform prophylactic oophorectomy should be approached with great caution for the majority of women who are at low risk of developing ovarian cancer. Steroid sulfatase (EC 3.1.6.2, STS) hydrolyzes steroid sulfates, such as estrone sulfate to estrone which can be converted to steroids with potent estrogenic properties, that is, estradiol; STS activity is much higher in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. The biological roles of estrogens in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues". 17beta-hydroxysteroid dehydrogenases (EC 1.1.1.62, 17-HSDs) are enzymes involved in the formation of active sex steroids. estrone is interconverted by two enzymes 17-HSD types. Type 1 converts estrone to estradiol and Type 2 catalyzes the reverse reaction. (PMID: 17653961, 17513923, 17470679, 17464097). CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8887; ORIGINAL_PRECURSOR_SCAN_NO 8882 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8944; ORIGINAL_PRECURSOR_SCAN_NO 8942 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8923; ORIGINAL_PRECURSOR_SCAN_NO 8921 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8903; ORIGINAL_PRECURSOR_SCAN_NO 8901 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4817; ORIGINAL_PRECURSOR_SCAN_NO 4815 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4834; ORIGINAL_PRECURSOR_SCAN_NO 4832 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4774; ORIGINAL_PRECURSOR_SCAN_NO 4772 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4796; ORIGINAL_PRECURSOR_SCAN_NO 4794 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8953; ORIGINAL_PRECURSOR_SCAN_NO 8951 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 4804; ORIGINAL_PRECURSOR_SCAN_NO 4803 CONFIDENCE standard compound; INTERNAL_ID 859; DATASET 20200303_ENTACT_RP_MIX508; DATA_PROCESSING MERGING RMBmix ver. 0.2.7; DATA_PROCESSING PRESCREENING Shinyscreen ver. 0.8.0; ORIGINAL_ACQUISITION_NO 8970; ORIGINAL_PRECURSOR_SCAN_NO 8969 A trace constituent of plant tissues, e.g. seeds of date (Phoenix dactylifera) and pomegranate (Punica granatum). Estrone is found in many foods, some of which are cauliflower, sweet rowanberry, carrot, and coconut. G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03C - Estrogens > G03CA - Natural and semisynthetic estrogens, plain G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03C - Estrogens > G03CC - Estrogens, combinations with other drugs D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones > D004967 - Estrogens C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen CONFIDENCE standard compound; INTERNAL_ID 2391 COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS Estrone (E1) is a natural estrogenic hormone. Estrone is the main representative of the endogenous estrogens and is produced by several tissues, especially adipose tissue. Estrone is the result of the process of aromatization of androstenedione that occurs in fat cells[1][2]. Estrone (E1) is a natural estrogenic hormone. Estrone is the main representative of the endogenous estrogens and is produced by several tissues, especially adipose tissue. Estrone is the result of the process of aromatization of androstenedione that occurs in fat cells[1][2].
Estrone 3-sulfate
Estrone sulfate is a sulfated estrone derivative. Estrone sulfate acts as a long-lived reservoir that can be converted as needed to the more active estradiol (from estrone via 17 beta-hydroxysteroid dehydrogenase). Estrone Sulfate (E1S) is the most abundant circulating estrogen in non-pregnant women as well as normal men. Estrone is primarily synthesized from estrone sulfate. Estrone is an estrogenic hormone secreted by the ovaries and adipose tissues. Estrone is one of the three estrogens found in humans. The other two are estriol and estradiol. Estrone is the least prevalent of the three. Estradiol plays a critical role on reproductive and sexual functioning in women and it also affects other organs including the bones. Estriol is an estrogen that is prevalent primarily during pregnancy. [HMDB] Estrone sulfate is a sulfated estrone derivative. Estrone sulfate acts as a long-lived reservoir that can be converted as needed to the more active estradiol (from estrone via 17 beta-hydroxysteroid dehydrogenase). Estrone Sulfate (E1S) is the most abundant circulating estrogen in non-pregnant women as well as normal men. Estrone is primarily synthesized from estrone sulfate. Estrone is an estrogenic hormone secreted by the ovaries and adipose tissues. Estrone is one of the three estrogens found in humans. The other two are estriol and estradiol. Estrone is the least prevalent of the three. Estradiol plays a critical role on reproductive and sexual functioning in women and it also affects other organs including the bones. Estriol is an estrogen that is prevalent primarily during pregnancy. C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones
2-Hydroxyestradiol
2-Hydroxyestradiol (2-OHE2), also known as estra-1,3,5(10)-triene-2,3,17beta-triol, is an endogenous steroid, catechol estrogen. 2-Hydroxyestradiol belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Thus, 2-hydroxyestradiol is considered to be a steroid molecule. It is a metabolite of estradiol, as well as a positional isomer of estriol. Transformation of estradiol to 2-hydroxyestradiol is a major metabolic pathway of estradiol in the liver. 2-Hydroxyestradiol is generated from estradiol via several cytochrome P450 enzymes. Specifically, CYP1A2 and CYP3A4 are the major enzymes catalyzing the 2-hydroxylation of estradiol. Conversion of estradiol into 2-hydroxyestradiol has been detected in the liver, uterus, breast, kidney, brain, and pituitary gland, as well as the placenta. 2-Hydroxyestradiol binds, with a low affinity, to estrogen receptors. 2-Hydroxyestradiol has approximately 7\\% and 11\\% of the affinity of estradiol at the estrogen receptors (ERs) ERalpha and ERbeta, respectively (PMID: 9048584). 2-Hydroxyestradiol is a catechol estrogen and in this regard bears some structural resemblance to the catecholamines dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) (PMID: 447670). In accordance, 2-hydroxyestradiol has been found to interact with catecholamine systems. The steroid is known to compete with catecholamines for binding to catechol O-methyltransferase and tyrosine hydroxylase and to competitively inhibit these enzymes (PMID: 447670). Inactivity of COMT blocks inactivation of catechol hormones and catecholamine neurotransmitters. 2-Hydroxyestradiol is also reported to inhibit angiongensis and tumor cell growth (PMID: 9472688). 2-Hydroxyestradiol is generated from estradiol by a Cytochrome P450. 2-Hydroxyestradiol binds, with a low affinity, to estrogen receptors. It inhbits catechol-O-methyltransferase (COMT) activity. Inactivity of COMT blocks inactivation of catechol hormones and catecholamine neutransmitters. 2-Hydroxyestradiol is also reported to inhibit angiongensis and tumor cell growth (PMID: 9472688). [HMDB] C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones
Estradiol
Estradiol is the most potent form of mammalian estrogenic steroids. Estradiol is produced in the ovaries. The ovary requires both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to produce sex steroids. LH stimulates the cells surrounding the follicle to produce progesterone and androgens. The androgens diffuse across the basement membrane to the granulosa cell layer, where, under the action of FSH, they are aromatized to estrogens, mainly estradiol. The ovary shows cyclical activity, unlike the testis that is maintained in a more or less constant state of activity. Hormone secretions vary according to the phase of the menstrual cycle. In the developing follicle LH receptors (LH-R) are only located on the thecal cells and FSH receptors (FSHR) on the granulosa cells. The dominant pre-ovulatory follicle develops LH-Rs on the granulosa cells prior to the LH surge. Thecal cells of the preovulatory follicle also develop the capacity to synthesize estradiol and this persists when the thecal cells become incorporated into the corpus luteum. After ovulation, the empty follicle is remodelled and plays an important role in the second half or luteal phase of the menstrual cycle. This phase is dominated by progesterone and, to a lesser extent, estradiol secretion by the corpus luteum. estradiol is also synthesized locally from cholesterol through testosterone in the hippocampus and acts rapidly to modulate neuronal synaptic plasticity. Localization of estrogen receptor alpha (ERalpha) in spines in addition to nuclei of principal neurons implies that synaptic ERalpha is responsible for rapid modulation of synaptic plasticity by endogenous estradiol. estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and hepatic stellate cells activation by inhibiting a generation of reactive oxygen species in primary cultures. This suggests that the greater progression of hepatic fibrosis and hepatocellular carcinoma in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. estradiol has been reported to induce the production of interferon (INF)-gamma in lymphocytes, and augments an antigen-specific primary antibody response in human peripheral blood mononuclear cells. IFN-gamma is a potent cytokine with immunomodulatory and antiproliferative properties. Therefore, female subjects, particularly before menopause, may produce antibodies against hepatitis B virus e antigen and hepatitis B virus surface antigen at a higher frequency than males with chronic hepatitis B virus infection. The estradiol-Dihydrotestosterone model of prostate cancer (PC) proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol. (PMID: 17708600, 17678531, 17644764). G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03C - Estrogens > G03CA - Natural and semisynthetic estrogens, plain D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones > D004967 - Estrogens COVID info from COVID-19 Disease Map, clinicaltrial, clinicaltrials, clinical trial, clinical trials C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen Growth promoter for livestock. Permitted in the USA Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS Estradiol (β-Estradiol) is a steroid hormone and the major female sex hormone. Estradiol can up-regulate the expression of neural markers of human endometrial stem cells (hEnSCs) and promote their neural differentiation. Estradiol can be used for the research of cancers, neurodegenerative diseases and neural tissue engineering[1][2]. Estradiol (β-Estradiol) is a steroid hormone and the major female sex hormone. Estradiol can up-regulate the expression of neural markers of human endometrial stem cells (hEnSCs) and promote their neural differentiation. Estradiol can be used for the research of cancers, neurodegenerative diseases and neural tissue engineering[1][2].
Estrone glucuronide
Estrone-glucuronide is the dominant metabolite of estradiol. Estrone glucuronide is formed by a UDP glucuronyltransferase (EC 2.4.1.17, UTP) reaction creating a much more water-soluble form of the hormone; glucuronides are the most abundant estrogen conjugates. Measurement of estrone-glucuronide is used as one reference method for determining ovulation (immunotubes are available for measuring urinary estrone glucuronide in conjunction with LH, one of the most advanced of ovulation prediction products). (PMID: 14742773, 1755456) [HMDB] Estrone-glucuronide is the dominant metabolite of estradiol. Estrone glucuronide is formed by a UDP glucuronyltransferase (EC 2.4.1.17, UTP) reaction creating a much more water-soluble form of the hormone; glucuronides are the most abundant estrogen conjugates. Measurement of estrone-glucuronide is used as one reference method for determining ovulation (immunotubes are available for measuring urinary estrone glucuronide in conjunction with LH, one of the most advanced of ovulation prediction products). (PMID: 14742773, 1755456). D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones CONFIDENCE Reference Standard (Level 1); INTERNAL_ID 8325
Estriol
Estriol is a metabolite of estrone metabolized via 16alpha-hydroxyestrone through the enzyme 16alpha-hydroxysteroid dehydrogenase (EC 1.1.1.147) or to 2- or 4-hydroxyestrone (catechol estrogens) by the action of catecho-O-methyltransferase (EC 2.1.1.6). The latter metabolites can be formed in the brain and may compete with receptors for catecholamines. Metabolites are conjugated with sulfate or glucuronide before excretion by the kidney. During pregnancy, estriol constitutes 60-70\\\\% of the total estrogens, increasing to 300-500-fold in relation to non-pregnant women. The late term human fetus produces relatively large amounts of 16 alphahydroxy DHEA, which serves the mother as a precursor of estriol. It has been shown that 90\\\\% of the precursors for the formation of estriol are of fetal origin. If abnormal maternal serum screening results, specifically low levels of unconjugated estriol in the second trimester are detected, a diagnosis of Smith-Lemli-Opitz syndrome (SLOS),or RSH is suspected. SLOS is an autosomal recessive disorder caused by mutations of the gene encoding 7-dehydrocholesterol reductase (EC 1.3.1.21, DHCR7). (PMID: 16202579, 16112271, 16097001). G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03C - Estrogens > G03CA - Natural and semisynthetic estrogens, plain G - Genito urinary system and sex hormones > G03 - Sex hormones and modulators of the genital system > G03C - Estrogens > G03CC - Estrogens, combinations with other drugs Estriol (also oestriol) is one of the three main estrogens produced by the human body. Estriol is found in common bean and pomegranate. C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS Estriol is a G protein-coupled estrogen receptor antagonist that can act on estrogen receptor-negative breast cancer cells. Estriol is a G protein-coupled estrogen receptor antagonist that can act on estrogen receptor-negative breast cancer cells.
2-Hydroxyestrone
2-Hydroxyestrone (2-OHE1), also known as estra-1,3,5(10)-trien-2,3-diol-17-one, is an endogenous, naturally occurring catechol estrogen and a major metabolite of estrone and estradiol. 2-Hydroxyestrone belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Thus, 2-Hydroxyestrone is considered to be a steroid molecule. It is formed irreversibly from estrone in the liver and to a lesser extent in other tissues via 2-hydroxylation mediated by cytochrome P450 enzymes, mainly the CYP3A and CYP1A subfamilies. 2-OHE1 is the most abundant catechol estrogen in the body. 2-Hydroxyestrone is found in all vertebrates. Vertebrates, especially mammals, metabolizes estrogen into two major pathways and one minor. The two major pathways lead to 2-hydroxyestrone and 16a-hydroxyestrone (2-OHE1 and 16a OHE1, respectively). The minor pathway leads to 4-hydroxyestrone (4-OHE1). 2a-hydroxyestrone is considered to be the good steroid metabolite (PMID: 8943806) as 2-hydroxyestrone does not stimulate cell growth and it blocks the action of stronger estrogens that may be carcinogenic. 2-hydroxyestrone is not significantly uterotrophic, whereas other hydroxylated estrogen metabolites including 2-hydroxyestradiol, 16a-hydroxyestrone, estriol, 4-hydroxyestradiol, and 4-hydroxyestrone all are. A low urinary ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone is a strong predictor of breast cancer risk among women (PMID: 19502596). Estrone (also oestrone) is an estrogenic hormone secreted by the ovary. Its molecular formula is C18H22O2. estrone has a melting point of 254.5 degrees Celsius. estrone is one of the three estrogens, which also include estriol and estradiol. estrone is the least prevalent of the three hormones, estradiol being prevalent almost always in a female body, estriol being prevalent primarily during pregnancy. estrone sulfate is relevant to health and disease due to its conversion to estrone sulfate, a long-lived derivative of estrone. estrone sulfate acts as a pool of estrone which can be converted as needed to the more active estradiol. [HMDB] C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C1636 - Therapeutic Steroid Hormone C147908 - Hormone Therapy Agent > C548 - Therapeutic Hormone > C483 - Therapeutic Estrogen D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones D020011 - Protective Agents > D016588 - Anticarcinogenic Agents D000970 - Antineoplastic Agents
2-Methoxy-estradiol-17b 3-glucuronide
2-Methoxy-estradiol-17beta 3-glucuronide is a natural human metabolite of 2-Methoxy-estradiol-17beta generated in the liver by UDP glucuonyltransferase. Glucuronidation is used to assist in the excretion of toxic substances, drugs or other substances that cannot be used as an energy source. Glucuronic acid is attached via a glycosidic bond to the substance, and the resulting glucuronide, which has a much higher water solubility than the original substance, is eventually excreted by the kidneys. 2-Methoxy-estradiol-17beta 3-glucuronide is a natural human metabolite of 2-Methoxy-estradiol-17beta generated in the liver by UDP glucuonyltransferase.
2-Methoxyestrone 3-glucuronide
2-Methoxyestrone 3-glucuronide belongs to the class of organic compounds known as steroid glucuronide conjugates. These are sterol lipids containing a glucuronide moiety linked to the steroid skeleton. Thus, 2-methoxyestrone 3-glucuronide is considered to be a steroid conjugate lipid molecule. 2-Methoxyestrone 3-glucuronide is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. 2-Methoxyestrone 3-glucuronide is a natural human metabolite of 2-methoxyestrone generated in the liver by UDP glucuronosyltransferase. 2-Methoxyestrone is a metabolite of 2-hydroxyestrone (a nonuterotrophic metabolite of estradiol). Glucuronidation is used to assist in the excretion of toxic substances, drugs, or other substances that cannot be used as an energy source. Glucuronic acid is attached via a glycosidic bond to the substance, and the resulting glucuronide, which has a much higher water solubility than the original substance, is eventually excreted by the kidneys. 2-Methoxyestrone 3-glucuronide is a natural human metabolite of 2-Methoxyestrone generated in the liver by UDP glucuonyltransferase. A glucuronide conjugate of 2-methodxyestrone formed by UDP-glucuronylstransferase (UTP). 2-methoxyestrone is a metabolite of 2-hydroxyestrone (a nonuterotrophic metabolite of estradiol) D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones
4-Hydroxyestradiol
4-Hydroxyestradiol is an oncogenic catechol estrogen produced by metabolism of Estrogen. D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones A human metabolite taken as a putative food compound of mammalian origin [HMDB]
17-beta-Estradiol-3-glucuronide
17beta-Estradiol 3-glucuronide belongs to the class of organic compounds known as steroid glucuronide conjugates. These are sterol lipids containing a glucuronide moiety linked to the steroid skeleton. 17beta-Estradiol 3-glucuronide is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. Estradiol glucuronide is believed to play an important role in the mechanism of 17beta-estradiol(E2)-mediated tumour formation. Conjugation with glucuronic acid lowers tissue levels by facilitating excretion. Heterotropic activation by daidzein appears to be specific for the glucuronidation of E2 because daidzein did not affect the glucuronidation of the 2- and 4-hydroxy metabolites of E2 (PMID: 16598814). Estradiol glucuronide is believed to play important roles in the mechanism of 17beta-estradiol(E2)-mediated tumor formation. Conjugation with glucuronic acid lowers tissue levels by facilitating excretion.The heterotropic activation by daidzein appears to be specific for the glucuronidation of E2 because daidzein did not affect the glucuronidation of the 2- and 4-hydroxy metabolites of E2. (PMID: 16598814) [HMDB] D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones