Prostaglandins are important regulators of reproductive function. In particular, prostaglandin F2␣ (PGF 2␣ ) 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 20␣-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 20␣-hydroxysteroid dehydrogenase gene was strongly expressed in the endometrium at the time of luteolysis. The corresponding recombinant enzyme has a K m of 7 M for PGH 2 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 PGF 2␣ . Taken together, these data point to this newly identified enzyme as the functional endometrial PGFS.Prostaglandins are local mediators acting through paracrine or autocrine mechanisms. Prostaglandins are produced from arachidonic acid liberated from phospholipid stores through the action of phospholipases. Arachidonic acid is then converted into prostaglandin H 2 (PGH 2 ), 1 the common precursor of all prostaglandins, through the cyclooxygenase and peroxydase activities of prostaglandin H synthase (PGHS). There are two PGHS: PGHS1 and PGHS2. These enzymes (also known as Cox-1 and Cox-2), which have been identified some 10 years ago, are still extensively studied. Because PGH 2 is the common precursor of all subtypes of prostaglandins and because these prostaglandin isotypes cause different and even opposing actions, the pathways leading to their individual formation need to be identified.Prostaglandin F2␣ (PGF 2␣ ) is involved in several physiological processes including pressure regulation in the eye (1), vasoconstriction (2), and renal filtration (3). It is associated with diseases such as diabetes (4), osteoporosis (5, 6), and menstrual disorder (7). However, it is mostly known for its effect on the female reproductive system. In mice, gene knockout of the FP receptor (the receptor for PGF 2␣ ) leads to a failure in the initiation of labor (8). For most mammalian species, the production of PGF 2␣ by the uterus is involved in the regulation of the ovarian cycle. This prostaglandin acts on the corpus luteum, initiating its regression (luteolysis) and leading to termination of the estrous cycle or of pregnancy (reviewed in Ref. 9). The regulation of PGF 2␣ production at the critical period of luteolysis or recognition of pregnancy has been studied extensively in ruminants. In cattle, PGF 2␣ is mainly synthesized by epit...

The human aldose reductase AKR1B1 currently associated with diabetes complications is also a highly functional PGF synthase responsible for PGF2α production in the human endometrium and a potential target for treatment of menstrual disorders.

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