Coordinate Expression of Anticoagulant Heparan Sulfate Proteoglycans and Serine Protease Inhibitors in the Rat Ovary: A Potent System of Proteolysis Control
During the reproductive cycle, ovarian follicles undergo major tissue-remodeling involving vascular changes and proteolysis. Anticoagulant heparan sulfate proteoglycans (aHSPGs) are expressed by granulosa cells during the development of the ovarian follicle. The function of aHSPGs in the ovary is un...
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Veröffentlicht in: | Biology of reproduction 2002-01, Vol.66 (1), p.144-158 |
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Zusammenfassung: | During the reproductive cycle, ovarian follicles undergo major tissue-remodeling involving vascular changes and proteolysis.
Anticoagulant heparan sulfate proteoglycans (aHSPGs) are expressed by granulosa cells during the development of the ovarian
follicle. The function of aHSPGs in the ovary is unknown, but they might be involved in proteolysis control through binding
and activation of serine protease inhibitors. To identify functional interactions between aHSPGs and heparin-binding protease
inhibitors in the follicle, we have coordinately localized aHSPGs, antithrombin III, protease nexin-1, and plasminogen activator
inhibitor-1 in the rat ovary during natural and gonadotropin-stimulated cycles. Anticoagulant HSPGs were visualized by autoradiography
of cryosections incubated with 125 I-antithrombin III, and protease inhibitors were assessed by immunohistochemistry and Northern blot hybridization. Anticoagulant
HSPGs were expressed in follicles before ovulation, were transiently decreased in postovulatory follicles, and were abundant
in the corpus luteum, mainly on capillaries. Anticoagulant HSPGs were colocalized with protease nexin-1 in follicles from
the early antral stage until ovulation, with antithrombin III in the preovulatory stage and after ovulation, and with plasminogen
activator inhibitor-1 in the corpus luteum. These data demonstrate that aHSPGs are critically expressed in the ovary to interact
sequentially with protease nexin-1, antithrombin III, and plasminogen activator inhibitor-1 during the cycle. The specificity
of these inhibitors is shifted toward thrombin inhibition in the presence of heparin, suggesting that aHSPGs direct their
action to control fibrin deposition in the follicle. The occupation of aHSPGs antithrombin-binding sites by mutant R393C antithrombin
III, injected in the ovarian bursa, decreased ovulation efficiency, further supporting the involvement of aHSPGs in the ovulation
process. |
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ISSN: | 0006-3363 1529-7268 |
DOI: | 10.1095/biolreprod66.1.144 |