Reduced Tuberoinfundibular Dopaminergic Neuronal Function in Rats with in situ Prolactin-Secreting Pituitary Tumors

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Abstract
Tuberoinfundibular dopaminergic (TIDA) neuronal function in rats with spontaneous or estrogen-induced prolactin- (PRL-)secreting pituitary tumors (prolactinomas) was studied by assaying dopamine (DA) concentration in pituitary stalk blood and electrically induced release of 3H-DA from the median eminence in vitro. Old rats with spontaneous prolactinomas showed enlarged and hemorrhagic pituitaries and elevated serum PRL levels. These rats had reduced DA in pituitary stalk blood, showed significantly lower response to the DA-releasing drug, nomifensine, and exhibited reduced electrically induced 3H-DA release from the median eminence in vitro, when compared to corresponding values in young and old rats without prolactinomas. The dopamine agonist piribedil failed to reduce electrically induced 3H-DA release by the superfused median eminence from old rats with prolactinomas, but not from old and young rats without prolactinomas. Old rats without prolactinomas also showed higher serum PRL values and pituitary weight than young rats without prolactinomas. However, stalk blood DA values before and after nomifensine, electrically induced 3 H-DA release by the median eminence in vitro, and inhibition by piribedil of 3H-DA release in vitro were significantly lower in old rats without prolactinomas than in young rats without prolactinomas. Estrogen treatment of young ovariectomized rats for 5 months produced enlarged and hemorrhagic pituitaries and elevated serum PRL values, but reduced the content of stalk blood DA and electrically induced release of 3H-DA by the median eminence in vitro as compared with values in untreated young ovariectomized control rats. Estrogen-treated rats also showed no response to piribedil on in vitro 3H-DA release. These results suggest that (1) there is a reduction of functional TIDA neurons during aging which becomes more marked as the animals develop spontaneous prolactinomas, and (2) development of estrogen-induced prolactinomas in young rats is similarly associated with reduced function of TIDA neurons.