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Endocrinology Vol. 141, No. 2 710-721
Copyright © 2000 by The Endocrine Society


ARTICLES

Sertoli Cell Prostaglandin D2 Synthetase Is a Multifunctional Molecule: Its Expression and Regulation1

Eileen T. Samy, Jonathan C. H. Li, Josephine Grima, Will M. Lee, Bruno Silvestrini and C. Yan Cheng

The Population Council (E.T.S., J.C.H.L., J.G., C.Y.C.), New York, New York 10021; the Department of Zoology, University of Hong Kong (E.T.S., J.C.H.L., W.M.L.), Hong Kong, People’s Republic of China; and the Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza (B.S.), Rome 00185, Italy

Address all correspondence and requests for reprints to: C. Yan Cheng, Ph.D., The Population Council, 1230 York Avenue, New York, New York 10021. E-mail: yan{at}popcbr.rockefeller.edu

PGD2 synthetase (PGD-S; PGH2 D-isomerase; EC 5.3.99.2) is a bifunctional protein first identified in the mammalian brain. It acts as a PGD2-producing enzyme and a retinoid transporter. PGD-S is present in the testis, where its protein and messenger RNA levels are similar to those in the brain. In view of its diversified regulatory functions, we investigated its regulation using primary cultures of Sertoli cells in vitro to assess its role in the testis. When Sertoli cells were cultured in serum-free medium to allow the formation of specialized junctions, it was found that PGD-S expression increased steadily with time, coinciding with the formation of inter-Sertoli junctions in vitro. However, neither germ cells (using a Sertoli/germ cell ratio between 1:1 and 1:30 when Sertoli cells were cultured at a density of 5 x 104 cells/cm2) nor germ cell-conditioned medium affected the expression of Sertoli cell PGD-S in vitro. These results thus unequivocally demonstrated that germ cells do not play a role in regulating testicular PGD-S expression. Although FSH, dihydrotestosterone, and testosterone had no apparent effect on Sertoli cell PGD-S expression, the addition of progesterone (1 x 10-11 to 1 x 10-9 M) and T3 (1 x 10-11 to 1 x 10-9 M) to Sertoli cell cultures elicited a significant increase in PGD-S expression by as much as 4.5- and 2.5 fold, respectively. As PGD-S is a known retinoid transporter, the effects of all-trans-retinoic acid and all-trans-retinal on Sertoli cell PGD-S expression were also assessed. Both compounds were found to induce Sertoli cell PGD-S expression. In summary, PGD-S is a putative Sertoli cell product whose expression is regulated by progesterone, metabolites of vitamin A, and T3. In view of its dual biological properties, a study of its regulation and physiology will yield new insights into understanding its role in the testis.




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