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Transport and Inactivation of Prostanoids

المؤلف:  Norman, A. W., & Henry, H. L.

المصدر:  Hormones

الجزء والصفحة:  3rd edition , p180-181

2026-07-25

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Prostanoids are synthesized by nearly all tissues in the body and are released to act on the cells that made them or on those very close by. Because they are charged anions, these molecules do not diffuse well through the plasma membrane. The prostaglandin transporter (PGT) has been identified as a protein containing 12 membrane-spanning regions. It is effective in bringing extracellular prostanoids into the cell for inactivating, thereby playing an important role in signal termination. The exit of newly synthesized prostanoids from the cell may also be carried out by PGT, but a second protein, multidrug-resistance protein 4 (MRP4), a member of a subfamily of ABC (ATP binding cassette) transporters is very effective in this regard. Further details about the transport of prostaglandins, thromboxanes, and other lipid signaling molecules remain to be elucidated.

The most important catabolic step in removal of the active prostanoids is the oxidation of the hydroxyl group at carbon 15 to a ketone by prostagland in-15-dehydrogenase, 15-PGDH, which completely inactivates the prostanoid. This enzyme is highly expressed in the lungs, placenta, kidney, and spleen. The reduction of the double bond between carbons 13 and 14 by protaglandin reductase, which has a tissue distribution similar to that of 15-PGDH, is a further catabolic step for these compounds.

Some cancer cells, such as those found in the colon, exhibit high levels of cyclooxygenase and pro-tumorigenic PGE2. In this and similar contexts, 15-PGDH is considered to be a tumor suppressor because of its ability to inactivate PGE2.