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Agents that decrease gonadotropin-releasing hormone (GnRH) receptor internalization do not inhibit GnRH-mediated

W C Gorospe, P M Conn

    Endocrinology
    |January 1, 1987
    PubMed
    Summary
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    Gonadotrope desensitization to GnRH is not solely explained by receptor internalization. Immobilized GnRH analogs that are not internalized still cause desensitization, uncoupling receptor internalization from LH release.

    Area of Science:

    • Endocrinology
    • Molecular Cell Biology
    • Reproductive Biology

    Background:

    • Exposure to Gonadotropin-Releasing Hormone (GnRH) in pituitary cell cultures triggers gonadotropin release, receptor capping, internalization, and loss.
    • This exposure also leads to altered responsiveness of the target cell, a phenomenon known as desensitization.

    Purpose of the Study:

    • To investigate the relationship between the loss of gonadotrope secretory responsiveness to GnRH (desensitization) and the internalization of the GnRH-receptor complex.
    • To determine if GnRH receptor internalization is a necessary mechanism for GnRH-mediated desensitization.

    Main Methods:

    • Pituitary cell cultures were pretreated with vinblastine (to prevent receptor internalization) or a control medium.
    • Cells were then incubated with GnRH or a GnRH analog (free or immobilized on agarose) to induce desensitization.

    Related Experiment Videos

  • Receptor binding assays and Luteinizing Hormone (LH) release measurements were used to assess desensitization and receptor internalization.
  • Main Results:

    • Vinblastine did not affect GnRH-stimulated LH release or desensitization, indicating internalization is not required for initial response or desensitization.
    • An immobilized GnRH analog, which bound to the receptor but was not internalized, caused desensitization equivalent to the free analog.
    • Partial depletion of LH stores contributed to desensitization, particularly under conditions inhibiting GnRH-stimulated LH release (EGTA).

    Conclusions:

    • GnRH receptor internalization and LH release can occur independently, suggesting these processes can be uncoupled.
    • The loss of GnRH receptor by internalization is not sufficient to explain GnRH-mediated desensitization of gonadotropes.
    • Desensitization involves mechanisms beyond receptor internalization, potentially including intracellular signaling pathways and LH store depletion.