“Prostaglandin F2alpha”的意思、由来-开放百科全书

In domestic mammals, it is produced by the uterus when stimulated by oxytocin, in the event that there has been no implantation during the luteal phase. It acts on the corpus luteum to cause luteolysis, forming a corpus albicans and stopping the production of progesterone. Action of PGF_2α is dependent on the number of receptors on the corpus luteum membrane.

The PGF_2α isoform 8-iso-PGF_2α was found in significantly increased amounts in patients with endometriosis, thus being a potential causative link in endometriosis-associated oxidative stress.^[2]

Mechanism of action

PGF_2α acts by binding to the prostaglandin F2α receptor. It is released in response to an increase in oxytocin levels in the uterus, and stimulates both luteolytic activity and the release of oxytocin.^[3] Because PGF_2α is linked with an increase in uterine oxytocin levels, there is evidence that PGF_2α and oxytocin form a positive feedback loop to facilitate the degradation of the corpus luteum.^[4] PGF_2α and oxytocin also inhibit the production of progesterone, a hormone that facilitates corpus luteum development. Conversely, higher progesterone levels inhibit production of PGF_2α and oxytocin, as the effects of the hormones are in opposition to each other.

Pharmaceutical Use

When injected into the body or amniotic sac, PGF_2α can either induce labor or cause an abortion depending on the concentration used. In small doses (1–4 mg/day), PGF_2α acts to stimulate uterine muscle contractions, which aids in the birth process. However, during the second trimester and in higher concentrations (40 mg/day),^[5] PGF_2α can cause an abortion by degrading the corpus luteum, which nourishes the fetus in the womb. Since the fetus is not viable outside the womb by this time, the lack of sustenance starves and aborts the fetus after a day or two.

Synthesis

Industrial Synthesis

In 2012 a concise and highly stereoselective total synthesis of PGF_2α was described.^[6] The synthesis requires only seven steps, a huge improvement on the original 17-steps synthesis of Corey and Cheng,^[7] and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, with S-proline as an asymmetric catalyst.

Biosynthesis

In the body PGF_2α is synthesized in several distinct steps. First, Phospholipase A₂ (PLA₂) facilitates the conversion of phospholipids to Arachidonic Acid, the framework from which all prostaglandins are formed.^[8] The Arachidonic Acid then reacts with two Cyclooxygenase (COX) receptors, COX-1 and COX-2 to form Prostaglandin H₂, an intermediate. Lastly, the compound reacts with Aldose Reductase (AKR1B1) to form PGF_2α.^[8]

Analogues

References

1. ^{{Cite book|url=https://www.worldcat.org/oclc/824530529|title=The Merck index : an encyclopedia of chemicals, drugs, and biologicals.|date=2013|publisher=Royal Society of Chemistry|others=O'Neil, Maryadele J., Royal Society of Chemistry (Great Britain)|isbn=1849736707|edition=15th|location=Cambridge, UK|oclc=824530529}}
2. ^{{Cite journal| last1 = Sharma | first1 = I.| last2 = Dhaliwal | first2 = L.| last3 = Saha | first3 = S.| last4 = Sangwan | first4 = S.| last5 = Dhawan | first5 = V.| title = Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis| journal = Fertility and Sterility| volume = 94| issue = 1| pages = 63–70| year = 2010| pmid = 19324352| doi = 10.1016/j.fertnstert.2009.01.141}}
3. ^{{Cite journal|last=Samuelsson|first=B.|last2=Goldyne|first2=M.|last3=Granström|first3=E.|display-authors=etal|date=1978|title=Prostaglandins and thromboxanes|url=|journal=Annual Review of Biochemistry|volume=47|pages=997–1029|doi=10.1146/annurev.bi.47.070178.005025}}
4. ^{{Cite journal|last=Hooper|first=S.B.|last2=Watkins|first2=W.B.|last3=Thorburn|first3=G.D.|date=1986|title=Oxytocin, oxytocin associated neurophysin, and prostaglandin F2 a concentrations in the uteroovarian vein of pregnant and nonpregnant sheep.|url=|journal=Endocrinology|volume=119|pages=2590–2597|via=|doi=10.1210/endo-119-6-2590}}
5. ^{{Cite web|url=https://www.drugs.com/cons/dinoprost-tromethamine-injection.html.|title=Dinoprost tromethamine Injection Advanced Patient Information|date=2016|website=Truvn Health Analytics Inc.|archive-url=|archive-date=|dead-url=|access-date=November 2, 2017}}
6. ^{{Cite journal | last1 = Coulthard | first1 = G. | last2 = Erb | first2 = W. | last3 = Aggarwal | first3 = V. K. | doi = 10.1038/nature11411 | title = Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps | journal = Nature | volume = 489 | issue = 7415 | pages = 278–281 | year = 2012 | pmid = 22895192| pmc = }}
7. ^{{cite book|title=The Logic of Chemical Synthesis|first1=E.J.|last1=Corey|first2=X.M.|last2=Cheng|publisher=Wiley|year=1995}}
8. ^¹{{Cite journal|last=Fortier|first=M. A.|last2=Krishnaswamy|first2=K.|last3=Danyod|first3=G.|last4=Boucher-Kovalik|first4=S.|last5=Chapdalaine|first5=P.|date=August 2008|title=A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems|journal=Journal of Physiology and Pharmacology|volume=59 Suppl 1|pages=65–89|issn=1899-1505|pmid=18802217}}