Aprotinin Antagonizes the Binding of Human Chorionic Gonadotropih to Its Receptor

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Abstract
Aprotinin caused a dose-dependent inhibition of [125I]hCG binding to its receptor in plasma membranes prepared from luteinized rat ovaries. Displacement of [125I]hCG from its receptor by aprotinin was temperature dependent, with an ID50 of 300 .mu.M at 4.degree. C and an ID50 of 3700 .mu.M at 22.degree. C. Equilibrium binding data showed a decrease in the Ka for hCG in the presence of increasing concentrations of aprotinin; aprotinin had no effect on the number of binding sites. The rate of association of hCG with its receptor was markedly reduced in the presence of aprotinin, but aprotinin had little effect on the rate of dissociation. Control experiments established that aprotinin did not inhibit the binding of [125I]hCG to its receptor due to its lectin properties, an ionic effect, or some irreversible impairment of the receptor or hormone. Aprotinin did not inhibit hCG binding when the receptor was solubilized out of ovarian membranes with Triton X-100. Aprotinin inhibited the hCG-mediated activation of adenylate cyclase in rat ovarian plasma membranes in a dose-dependent manner. Similarly, aprotinin antagonized the hCG-stimulated biosynthesis of progesterone by dispersed rat luteal cells. The maximal agonistic activity of hCG was attenuated in these two bioassays. The data are compatible with a hypothesis that aprotinin sterically hinders the entry of hCG into its receptor site by binding to a protease in the plasma membrane that is closely associated with the hCG receptor. This proposal is consistent with the emerging concept that integral membrane proteases are modulators of receptor function.