Prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...

F_2α (PGF_2α in

prostanoid Prostanoids are active lipid mediators that regulate inflammatory response. Prostanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasocons ...

nomenclature), pharmaceutically termed carboprost is a naturally occurring prostaglandin used in medicine to induce labor and as an

abortifacient An abortifacient ("that which will cause a miscarriage" from Latin: '' abortus'' "miscarriage" and '' faciens'' "making") is a substance that induces abortion. This is a nonspecific term which may refer to any number of substances or medications, ...

. Prostaglandins are lipids throughout the entire body that have a hormone-like function. In pregnancy, PGF2 is medically used to sustain contracture and provoke myometrial ischemia to accelerate labor and prevent significant blood loss in labor. Additionally, PGF2 has been linked to being naturally involved in the process of labor. It has been seen that there are higher levels of PGF2 in maternal fluid during labor when compared to at term. This signifies that there is likely a biological use and significance to the production and secretion of PGF2 in labor. Prostaglandin is also used to treat uterine infections in domestic animals. In domestic mammals, it is produced by the uterus when stimulated by

oxytocin Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytoc ...

, in the event that there has been no implantation during the luteal phase. It acts on the

corpus luteum The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...

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 Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, fa ...

, thus being a potential causative link in endometriosis-associated oxidative stress.

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. 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. PGF_2α and oxytocin also inhibit the production of

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the majo ...

, 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. This is directly exhibited following ovulation when there is a spike of progesterone levels, and then as progesterone levels decrease, PGF2 levels will peak.

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 first trimester and in higher concentrations (40 mg/day), PGF_2α can cause an abortion by degrading the corpus luteum, which normally acts to maintain pregnancy via the production of progesterone. Since the fetus is not viable outside the womb by this time, the lack of progesterone leads to the shedding of the uterine lining and the death of the fetus. However, this process is not fully understood.

Pyometra and uterine infections

Lutalyse is used for the treatment of

pyometra Pyometra or pyometritis is a uterine infection. Though it is most commonly known as a disease of the unaltered female dog, it is also a notable human disease. It is also seen in female cattle, horses, goats, sheep, swine, cats, rabbits, hamsters, ...

in domestic dogs and cats. The drug is also administered to dairy cows in order to reduce uterine infections.

Synthesis

Industrial Synthesis

In 2012 a concise and highly stereoselective total synthesis of PGF_2α was described. The synthesis requires only seven steps, a huge improvement on the original 17-steps synthesis of Corey and Cheng, and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, with ''S''-

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

as an asymmetric catalyst. In 2019, a more effective and stereoselective synthesis was described. The synthesis requires 5 steps to get to the intermediate which then undergoes a cross-metathesis reaction to install the E-alkene. Then, a Wittig reaction is performed to install the Z-alkene. Finally, the protecting groups are removed with acid. In the body PGF_2α is synthesized in several distinct steps. First, Phospholipase A₂ (PLA₂) facilitates the conversion of phospholipids to

Arachidonic Acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''ara ...

, the framework from which all prostaglandins are formed. The Arachidonic Acid then reacts with two

Cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...

(COX) receptors, COX-1 and COX-2, or PGH synthase to form Prostaglandin H₂, an intermediate. Lastly, the compound reacts with Aldose Reductase (

AKR1B1 Aldo-keto reductase family 1, member B1 (AKR1B1), also known as aldose reductase, is an enzyme that is encoded by the ''AKR1B1'' gene in humans. It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the red ...

) or PGF Synthase to form PGF_2α.

Analogues

The following medications are analogues of prostaglandin F_2α: *

Latanoprost Latanoprost, sold under the brand name Xalatan among others, is a medication used to treat increased pressure inside the eye. This includes ocular hypertension and open angle glaucoma. It is applied as eye drops to the eyes. Onset of effects is ...

Bimatoprost Bimatoprost, sold under the brand name Lumigan among others, is a medication used to treat high pressure inside the eye including glaucoma. Specifically it is used for open angle glaucoma when other agents are not sufficient. It may also be use ...

* Travoprost *

Carboprost Carboprost (INN, trade names for the tromethamine salts Hemabate, Tham) is a synthetic prostaglandin analogue of PGF2α (specifically, it is 15-methyl-PGF2α) with oxytocic properties. Carboprost's main use is in the obstetrical emergency of po ...

References

{{Prostanoidergics Abortifacients F2