A cDNA clone of prostaglandin F synthase (PGFS) was isolated from human lung by using cDNA of bovine lungtype PGFS as a probe and its protein expressed in Escherichia coli was purified to apparent homogeneity. The human PGFS catalyzed the reduction of prostaglandin (PG) D 2 , PGH 2 and phenanthrenequinone (PQ), and the oxidation of 9K K,11L L-PGF 2 to PGD 2 . The k cat /K m values for PGD 2 and 9K K,11L L-PGF 2 were 21 000 and 1800 min 31 mM 31 , respectively, indicating that the catalytic efficiency for PGD 2 and 9K K,11L L-PGF 2 was the highest among the various substrates, except for PQ. The PGFS activity in the cytosol of human lung was completely absorbed with antihuman PGFS antiserum. Moreover, mRNA of PGFS was expressed in peripheral blood lymphocytes and the expression in lymphocytes was markedly suppressed by the T cell mitogen concanavalin A. These results support the notion that human PGFS plays an important role in the pathogenesis of allergic diseases such as asthma.z 1999 Federation of European Biochemical Societies.

Although the secreted phospholipase A 2 (sPLA 2 ) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA 2 (sPLA 2 -X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA 2 -X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA 2 -X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA 2 -X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.

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