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Related Experiment Videos

Resistance to bromocriptine in prolactinomas.

I Pellegrini1, R Rasolonjanahary, G Gunz

  • 1Laboratoire de Neuroendocrinologie Expérimentale, INSERM U. 297, Marseille, France.

The Journal of Clinical Endocrinology and Metabolism
|September 1, 1989
PubMed
Summary

Bromocriptine resistance in prolactinoma patients is linked to reduced dopaminergic binding sites and altered adenylate cyclase activity. This explains why some patients do not respond to this dopamine agonist therapy.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Prolactinomas are pituitary tumors that secrete prolactin (PRL).
  • Bromocriptine, a dopamine agonist, is a primary treatment for prolactinomas, normalizing PRL secretion in many patients.
  • However, a subset of patients exhibits resistance to bromocriptine therapy.

Purpose of the Study:

  • To investigate the underlying mechanisms of bromocriptine resistance in patients with prolactinomas.
  • To compare cellular and molecular characteristics of bromocriptine-resistant prolactinoma cells with those from responsive patients.

Main Methods:

  • Cultured prolactinoma cells from resistant and responsive patients were used to assess PRL release in response to bromocriptine.
  • Dopaminergic binding site density was measured using [3H] spiroperidol in tumor cell membranes.

Related Experiment Videos

  • Adenylate cyclase activity was assessed in response to dopamine in different patient groups.

    • Main Results:

    • Prolactinoma cells from bromocriptine-resistant patients showed significantly less inhibition of PRL release compared to responsive controls.
    • Resistant tumors exhibited lower densities of dopaminergic binding sites, particularly in cases with tumor growth during therapy.
    • Dopamine's effect on adenylate cyclase varied, with paradoxical stimulation observed in tumors that grew during bromocriptine treatment.

    Conclusions:

    • Bromocriptine resistance in prolactinomas is associated with a deficiency in functional dopaminergic receptors.
    • Reduced dopaminergic binding sites and altered signal transduction pathways (adenylate cyclase activity) contribute to treatment failure.
    • These findings highlight potential targets for overcoming bromocriptine resistance in prolactinoma management.