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

Beatriz Collado, María J. Carmena, Joaquín Cortés, Andrew V Schally, Juan C. Prieto

Research output: Contribution to journalArticle

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 alphas and alphai 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 alphas and a modest increase of alphai G-protein subunit levels in ovary, a marked increase of alphas and alphai levels in breast, and a lack of effect on alphas/alphai 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.

Original languageEnglish
Pages (from-to)725-730
Number of pages6
JournalInternational Journal of Oncology
Volume24
Issue number3
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Hormone Antagonists
Protein Subunits
Adenylyl Cyclases
Gonadotropin-Releasing Hormone
Ovary
Breast
Vasoactive Intestinal Peptide
G-Protein-Coupled Receptors
Peptides
Signal Transduction
GTP-Binding Protein alpha Subunits
cetrorelix
Ovariectomy
Gynecology
GTP-Binding Proteins
Western Blotting
Cell Proliferation
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Luteinizing hormone-releasing hormone antagonist Cetrorelix regulates the expression of Galphas and Galphai protein subunits and adenylate cyclase activity in rat ovary, breast and pituitary. / Collado, Beatriz; Carmena, María J.; Cortés, Joaquín; Schally, Andrew V; Prieto, Juan C.

In: International Journal of Oncology, Vol. 24, No. 3, 01.03.2004, p. 725-730.

Research output: Contribution to journalArticle

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