“Estradiol glucuronide”的意思、由来-开放百科全书

When exogenous estradiol is administered orally, it is subject to extensive first-pass metabolism (95%) in the intestines and liver.^[2]^[3] A single administered dose of estradiol is absorbed 15% as estrone, 25% as estrone sulfate, 25% as estradiol glucuronide, and 25% as estrone glucuronide.^[2] Formation of estrogen glucuronide conjugates is particularly important with oral estradiol as the percentage of estrogen glucuronide conjugates in circulation is much higher with oral ingestion than with parenteral estradiol.^[2] Estradiol glucuronide can be converted back into estradiol, and a large circulating pool of estrogen glucuronide and sulfate conjugates serves as a long-lasting reservoir of estradiol that effectively extends its elimination half-life of oral estradiol.^[2] In demonstration of the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol,^[2] the elimination half-life of oral estradiol is 13 to 20 hours^[4] whereas with intravenous injection its elimination half-life is only about 1 to 2 hours.^[5]

Approximately 7% of estradiol is excreted in the urine as estradiol glucuronide.^[6]

Estradiol glucuronide is transported into prostate gland, testis, and breast cells by OATP1A2, OATP1B1, OATP1B3, OATP1C1, and OATP3A1.^[7] The ABC transporters MRP2, MRP3, MRP4, and BCRP, as well as several other transporters, have been found to transport estradiol glucuronide out of cells.^[7]^[8]

The circulating concentrations of estrogen glucuronides are generally more than 10-fold lower than those of estrone sulfate, the most abundant estrogen conjugate in the circulation.^[8]

Estradiol glucuronide has been identified as an agonist of the G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor.^[9] This may be involved in estradiol glucuronide-induced cholestasis.^[9]

Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens by β-glucuronidase in tissues that express this enzyme, such as the mammary gland.^[10] As a result, estrogen glucuronides have estrogenic activity via conversion into estrogens.^[10]

The positional isomer of estradiol glucuronide, estradiol 3-glucuronide, also occurs as a major endogenous metabolite of estradiol, circulating at two-thirds of the levels of estrone sulfate when it reaches its maximal concentrations just before ovulation and during the peak in estradiol levels that occurs at this time.^[11]

See also

References

1. ^¹²³http://www.hmdb.ca/metabolites/HMDB10317
2. ^¹²³⁴{{cite book|author1=Michael Oettel|author2=Ekkehard Schillinger|title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA268|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=268–}}
3. ^{{cite book|author1=M. Notelovitz|author2=P.A. van Keep|title=The Climacteric in Perspective: Proceedings of the Fourth International Congress on the Menopause, held at Lake Buena Vista, Florida, October 28–November 2, 1984|url=https://books.google.com/books?id=VM0hBQAAQBAJ&pg=PA406|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-4145-8|pages=406–}}
4. ^{{cite journal|last1=Stanczyk|first1=Frank Z.|last2=Archer|first2=David F.|last3=Bhavnani|first3=Bhagu R.|title=Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment|journal=Contraception|volume=87|issue=6|year=2013|pages=706–727|issn=0010-7824|doi=10.1016/j.contraception.2012.12.011}}
5. ^{{cite journal | vauthors = Düsterberg B, Nishino Y | title = Pharmacokinetic and pharmacological features of oestradiol valerate | journal = Maturitas | volume = 4 | issue = 4 | pages = 315–24 | year = 1982 | pmid = 7169965 | doi = | url = }}
6. ^{{cite book|author1=Kelly Smith|author2=Daniel M. Riche|author3=Nickole Henyan|title=Clinical Drug Data, 11th Edition|url=https://books.google.com/books?id=bi6-qSVcRZwC|date=15 April 2010|publisher=McGraw Hill Professional|isbn=978-0-07-162686-6}}
7. ^¹{{cite journal | vauthors = Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA | title = The Regulation of Steroid Action by Sulfation and Desulfation | journal = Endocr. Rev. | volume = 36 | issue = 5 | pages = 526–63 | date = October 2015 | pmid = 26213785 | doi = 10.1210/er.2015-1036 | url = }}
8. ^¹{{cite journal | vauthors = Järvinen E, Deng F, Kidron H, Finel M | title = Efflux transport of estrogen glucuronides by human MRP2, MRP3, MRP4 and BCRP | journal = J. Steroid Biochem. Mol. Biol. | volume = 178 | issue = | pages = 99–107 | date = April 2018 | pmid = 29175180 | doi = 10.1016/j.jsbmb.2017.11.007 | url = }}
9. ^¹{{cite journal | vauthors = Zucchetti AE, Barosso IR, Boaglio AC, Basiglio CL, Miszczuk G, Larocca MC, Ruiz ML, Davio CA, Roma MG, Crocenzi FA, Pozzi EJ | title = G-protein-coupled receptor 30/adenylyl cyclase/protein kinase A pathway is involved in estradiol 17ß-D-glucuronide-induced cholestasis | journal = Hepatology | volume = 59 | issue = 3 | pages = 1016–29 | date = March 2014 | pmid = 24115158 | doi = 10.1002/hep.26752 | url = }}
10. ^¹{{cite journal | vauthors = Zhu BT, Conney AH | title = Functional role of estrogen metabolism in target cells: review and perspectives | journal = Carcinogenesis | volume = 19 | issue = 1 | pages = 1–27 | date = January 1998 | pmid = 9472688 | doi = 10.1093/carcin/19.1.1 | url = }}
11. ^{{cite book|author1=F. A. Kincl|author2=J. R. Pasqualini|title=Hormones and the Fetus: Volume 1: Production, Concentration and Metabolism During Pregnancy|url=https://books.google.com/books?id=0ly2AgAAQBAJ&pg=PA39|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-8538-2|pages=39–}}

See also

References

External links