, Volume 3, Issue 4, pp 221–227 | Cite as

Decreased Cannabinoid CB1 Receptor mRNA Levels and Immunoreactivity in Pituitary Tumors Induced by Prolonged Exposure to Estrogens

  • Sara González
  • Mauriello Romanazzi
  • Fernando Berrendero
  • José A. Ramos
  • Maria Fosca Franzoni
  • Javier Fernández-Ruiz


Recent studies have demonstrated the occurrence of endocannabinoids and their CB1 receptor subtype in the anterior pituitary gland, despite previous evidence suggesting their exclusive presence and action in the neuroendocrine hypothalamus. The present study was designed to examine the potential changes in these CB1 receptors located in the anterior pituitary gland in three different experimental situations, which are known to affect anterior pituitary function: (i) estrogen-induced pituitary tumorization, (ii) presence of ectopic pituitaries, and (iii) chronic treatment with D1 or D2 dopaminergic receptor agonists or antagonists. Results were as follows. Induction of pituitary tumorization by implantation of silastic capsules containing diethylstilbestrol, a synthetic estrogen, produced the expected body weight loss and increase in pituitary weight and plasma prolactin (PRL) levels. In hyperplastic pituitaries, both CB1 receptor mRNA levels and immunoreactivity decreased significantly. Double labelling studies demonstrated that CB1 receptors colocalized, in pituitary tumors, with PRL- or luteinizing hormone-containing cells, as they did in normal pituitaries. Plasma PRL levels were also increased in rats bearing ectopic pituitaries implanted under the kidney capsule. As previously reported, this increase was originated by the hormone release from the ectopic gland, because the normotopic pituitary collaborated scarcely to elevate PRL levels since it was hypofunctional due to the activation of peripheral PRL-induced feedback mechanisms. However, in this hypofunctional anterior pituitary, there were not any changes in CB1 receptor mRNA levels and immunoreactivity. Finally, chronic treatment with SKF38393, a D1 receptor agonist, or bromocriptine, a D2 receptor agonist, or with their corresponding antagonists, SCH 23390 or sulpiride, respectively, did not alter CB1 receptor mRNA levels and immunoreactivity, although produced the expected changes in plasma PRL levels. In summary, estrogen-induced pituitary tumorization was associated with a marked reduction in CB1 receptors, despite the fact that these receptors were located, among others, on lactotroph cells which develop hyperplasia during tumor induction. Whether this decrease is associated with the ethiology of pituitary tumor induction and whether their pharmacological activation might affect tumorization process are presently unknown, but this will be subjected of further research.

CB1 receptors cannabinoid anterior pituitary gland pituitary tumors DES prolactin 


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Sara González
    • 1
  • Mauriello Romanazzi
    • 2
  • Fernando Berrendero
    • 1
  • José A. Ramos
    • 1
  • Maria Fosca Franzoni
    • 2
  • Javier Fernández-Ruiz
    • 3
  1. 1.Departamento de Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad ComplutenseMadridSpain
  2. 2.Dipartimento di Biologia Animale e dell'Uomo, Laboratorio di Anatomia ComparataUniversitá degli Studi di TorinoTorinoItaly
  3. 3.Departamento de Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad ComplutenseMadridSpain

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