Nerve Growth Factor Suppresses the Tumoral Phenotype of Human Prolactinomas

Abstract

We summarize here our data showing that various phenotypical characteristics distinguish prolactinoma cell lines obtained from responder and nonresponder patients, as defined by their responses to bromocriptine administration. Nonresponder cell lines have a higher degree of malignancy than responder cells and do not express D₂ receptors for dopamine. Both cell lines express NGF receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in vitro and when transplanted in vivo in nude mice, results in their differentiation into the responder phenotype reexpressing D₂ receptors. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

Hormonal control of pituitary prolactin-secreting tumors

“…There are two general classes of prolactinomas, those which respond to treatment with a dopamine agonist with a cessation of lactotropic proliferation and those that do not. The nonresponsive tumors lack D2 receptors on the lactotropes and express low levels of NGF (116). Recently, it has been demonstrated that lactotropes from a non-responsive tumor, became responsive to dopamine agonist therapy after treatment with NGF, which caused the expression of the D2 receptors (117).…”