Decreased cannabinoid CB1 receptor mRNA levels and immunoreactivity in pituitary hyperplasia induced by prolonged exposure to estrogens.

Recent studies have demonstrated that cannabinoid CB1 receptor gene expression in the anterior pituitary gland is under the influence of estrogens. Because these receptors have been recently involved in the development of several types of cancer, it would be interesting to examine the changes produced in these receptors by the development of pituitary hyperplasia after a chronic exposure to estrogens. To this end, we measured mRNA levels and immunoreactivity for the CB1 receptor in the anterior pituitary gland of rats implanted with silastic capsules containing diethylstilbestrod (DES), a synthetic estrogen, or empty capsules. Results were as follows. Induction of pituitary hyperplasia with DES produced the expected body weight loss (-38.4%) and increase in pituitary weight (5-fold) and plasma prolactin (PRL) levels (90-fold). In hyperplastic pituitaries, both CB1 receptor mRNA levels and immunoreactivity decreased significantly (-79.4% and -63.2% respectively). Double immuno-labelling studies demonstrated that CB1 receptors colocalized, in hyperplastic pituitaries, with PRL- or luteinizing hormone-containing cells, as they did in normal pituitaries. In summary, estrogen-induced pituitary hyperplastia 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 DES exposure. Whether this decrease is involved in the ethiology of pituitary hyperplasia and whether the pharmacological activation of these receptors might affect this process are presently unknown, but this will be subjected of further research.