Luteinizing hormone-releasing hormone antagonist Cetrorelix regulates the expression of Gαs and Gαi protein subunits and adenylate cyclase activity in rat ovary, breast and pituitary

  • Authors:
    • Beatriz Collado
    • María J. Carmena
    • Joaquín Cortés
    • Andrew V. Schally
    • Juan C. Prieto
  • View Affiliations

  • Published online on: March 1, 2004     https://doi.org/10.3892/ijo.24.3.725
  • Pages: 725-730
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Abstract

The mechanisms by which luteinizing hormone-releasing hormone (LH-RH) antagonists act on extra-pituitary tissues are poorly understood. In view of extensive use of Cetrorelix in gynecology and oncology, we investigated its effects on signal transduction pathways of G-protein coupled receptors and adenylate cyclase which are involved in a huge array of cellular events including normal and pathological cell proliferation. Thirty days after a single i.m. injection of 3 mg Cetrorelix pamoate depot to female rats, normal or ovariectomized, we evaluated the effects of this chronic treatment on the expression of αs and αi G-protein subunits in the ovary, breast and pituitary, as well as the adenylate cyclase response in vitro to LH-RH, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP). Varied patterns of response to Cetrorelix, depending on the gland and estrogenic status were observed. Western blot analysis showed a modest decrease of αs and a modest increase of αi G-protein subunit levels in ovary, a marked increase of αs and αi levels in breast, and a lack of effect on αs/αi levels in pituitary. In the ovary, adenylate cyclase activity was not changed by in vitro addition of LH-RH, but the responses to VIP and PACAP increased after Cetrorelix treatment. In the breast, chronic administration of the LH-RH antagonist decreased the adenylate cyclase response to PACAP, which returned to normal after ovariectomy. In the pituitary, Cetrorelix abolished the stimulatory effect of VIP upon adenylate cyclase activity. Thus, the LH-RH antagonist Cetrorelix exerted selective modifications at different steps of the G-protein coupled receptors/adenylate cyclase system of signal transduction in the rat ovary, breast and pituitary.

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March 2004
Volume 24 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Collado, B., Carmena, M.J., Cortés, J., Schally, A.V., & Prieto, J.C. (2004). Luteinizing hormone-releasing hormone antagonist Cetrorelix regulates the expression of Gαs and Gαi protein subunits and adenylate cyclase activity in rat ovary, breast and pituitary. International Journal of Oncology, 24, 725-730. https://doi.org/10.3892/ijo.24.3.725
MLA
Collado, B., Carmena, M. J., Cortés, J., Schally, A. V., Prieto, J. C."Luteinizing hormone-releasing hormone antagonist Cetrorelix regulates the expression of Gαs and Gαi protein subunits and adenylate cyclase activity in rat ovary, breast and pituitary". International Journal of Oncology 24.3 (2004): 725-730.
Chicago
Collado, B., Carmena, M. J., Cortés, J., Schally, A. V., Prieto, J. C."Luteinizing hormone-releasing hormone antagonist Cetrorelix regulates the expression of Gαs and Gαi protein subunits and adenylate cyclase activity in rat ovary, breast and pituitary". International Journal of Oncology 24, no. 3 (2004): 725-730. https://doi.org/10.3892/ijo.24.3.725