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Endocrinology, doi:10.1210/en.2008-0697
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Endocrinology Vol. 150, No. 1 413-421
Copyright © 2009 by The Endocrine Society

Induction of Heparanase in Bovine Granulosa Cells by Luteinizing Hormone: Possible Role during the Ovulatory Process

Eyal Klipper, Ehud Tatz, Tatiana Kisliouk, Israel Vlodavsky, Uzi Moallem, Dieter Schams, Yaniv Lavon, David Wolfenson and Rina Meidan

Department of Animal Sciences (E.K., E.T., T.K., Y.L., D.W., R.M.), Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; Cancer and Vascular Biology Research Center (I.V.), The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel; Department of Dairy Cattle (U.M.), Institute of Animal Sciences, Volcani Center, Bet-Dagan 5025O, Israel; and Institute of Physiology (D.S.), Weihenstephan, Technical University of Munich, 85350 Freising-Weihenstephan, Germany

Address all correspondence and requests for reprints to: Rina Meidan, Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel. E-mail: rina.meidan{at}huji.ac.il.

Follicular development, follicular rupture, and corpus luteum (CL) formation are accompanied by extensive tissue remodeling. We examined whether heparanase (HPSE), which cleaves heparan sulfate glycosaminoglycans, is induced during these processes. Prostaglandin F2{alpha} injection, which initiated luteolysis and the development of a preovulatory follicle, moderately increased HPSE mRNA in bovine granulosa cells (GCs). GnRH, used to induce gonadotropin surge, markedly augmented HPSE mRNA levels 12 h after its injection. The temporal pattern of HPSE gene expression in follicular-luteal transition was further examined in follicles collected before, and 4, 10, 20, 25, and 60 h after GnRH injection. HPSE mRNA increased transiently 10–20 h after GnRH injection to levels 10-fold higher than in untreated heifers. HPSE protein levels were similarly elevated 20 h after GnRH injection in GCs, but not in the theca layer. Cyclooxygenase-2 (PTGS2) mRNA peaked before ovulation when HPSE levels returned to baseline levels. HPSE mRNA abundance also remained low in the CLs. The antiprogesterone, RU-486, elevated HPSE levels in GC culture, suggesting that progesterone secreted by CLs may inhibit HPSE. HPSE immunostaining was more abundant in GCs than thecae. In cultured GCs, LH induced a transient increase in HPSE mRNA 3–6 h after its addition, but not at 24 h. However, PTGS2 mRNA was clearly induced at this time. These findings suggest that: 1) HPSE may play a role in ovulation but much less so during CL development, and 2) GC-derived HSPE may be a novel member of the LH-induced extracellular matrix-degrading enzyme family and may contribute to follicular rupture.







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