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Originally published In Press as doi:10.1074/jbc.M208318200 on January 24, 2003

J. Biol. Chem., Vol. 278, Issue 13, 11205-11212, March 28, 2003
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An Aldose Reductase with 20alpha -Hydroxysteroid Dehydrogenase Activity Is Most Likely the Enzyme Responsible for the Production of Prostaglandin F2alpha in the Bovine Endometrium*

Eric MadoreDagger , Nathalie Harvey, Julie Parent, Pierre Chapdelaine, Joe A. Arosh, and Michel A. Fortier§

From the Unité de Recherche en Ontogénie et Reproduction et Département d'Obstétrique et Gynécologie, Centre Hospitalier Universitaire de Québec, Université Laval, Sainte-Foy, Québec G1V 4G2, Canada

Prostaglandins are important regulators of reproductive function. In particular, prostaglandin F2alpha (PGF2alpha ) is involved in labor and is the functional mediator of luteolysis to initiate a new estrous cycle in many species. These actions have been extensively studied in ruminants, but the enzymes involved are not clearly identified. Our objective was to identify which prostaglandin F synthase is involved and to study its regulation in the endometrium and in endometrial primary cell cultures. The expression of all previously known prostaglandin F synthases (PGFSs), two newly discovered PGFS-like genes, and a 20alpha -hydroxysteroid dehydrogenase was studied by Northern blot and reverse transcription PCR. These analyses revealed that none of the known PGFS or the PGFS-like genes were significantly expressed in the endometrium. On the other hand, the 20alpha -hydroxysteroid dehydrogenase gene was strongly expressed in the endometrium at the time of luteolysis. The corresponding recombinant enzyme has a Km of 7 µM for PGH2 and a PGFS activity higher than the lung PGFS. This enzyme has two different activities with the ability to terminate the estrous cycle; it metabolizes progesterone and synthesizes PGF2alpha . Taken together, these data point to this newly identified enzyme as the functional endometrial PGFS.

* This work was supported by grants from the Canadian Institutes for Health Research and Natural Sciences and Engineering Research Council of Canada.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Recipient of a Wyeth-Ayerst/Canadian Institutes for Health Research postdoctoral fellowship.

§ To whom correspondence should be addressed: Unité de Recherche en Ontogénie et Reproduction, Centre Hospitalier Universitaire de Québec, Université Laval, 2705, Boul. Laurier, Sainte-Foy, Québec G1V 4G2, Canada. Tel.: 418-656-4141 (ext. 6141); Fax: 418-654-2714; E-mail: mafortier@crchul.ulaval.ca.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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