Gonatropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture

Hebrew University of Jerusalem, Yerushalayim, Jerusalem, Israel
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 06/1993; 76(5):1101-5. DOI: 10.1210/jc.76.5.1101
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We investigated the effect of gonadotropins on protease that were suggested to be implicated in the invasive activity of the trophoblast. hCG levels ranging from 10 x 10(3) to 333 x 10(3) IU/L produced a dose-dependent inhibition of the in vitro globinolytic activity of the purified proteases trypsin, chymotrypsin, and urokinase, but failed to inhibit plasmin, collagenase, elastase, and tissue-type plasminogen activator. Likewise, FSH inhibited purified trypsin and urokinase, but not plasmin or tissue-type plasminogen activator. Culture medium conditioned with human trophoblast displayed serine protease and urokinase-like activities; exposure of the cultured trophoblast to exogenous hCG markedly suppressed serine protease and urokinase activities in the conditioned medium. A short treatment of the conditioned medium with trypsin abolished the hCG-mediated inhibition of urokinase activity. The present findings offer an explanation for earlier observations that hCG reduced collagenase activity in trophoblasts without affecting the level of collagenase-specific mRNA. The present results are also consistent with the concept that hCG, by its direct ability to inhibit certain serine proteases and urokinase in trophoblast, suppresses a protease-mediated conversion of procollagenase to active collagenase. The ability of hCG to prevent initiation of the collagenolytic cascade suggests that gonadotropins may regulate the transient invasive activity of the trophoblast.

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    • "These apparently discordant effects of hCG on trophoblast function may be explained by the fact that the previous studies evaluated only the migratory effects, whereas we have assessed the invasive potential of the cells, including ECM remodelling and cell motility . In addition, other in vitro studies using primary trophoblast cultures have demonstrated that hCG decreases trophoblast cell invasiveness (Milwidsky et al., 1993; Yagel et al., 1993). "
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