Decline of tuberoinfundibular dopaminergic function resulting from chronic hyperprolactinemia in rats

The effect of hyperprolactinemia on tuberoinfundibular dopaminergic (TIDA) neurons was studied after sc transplantation of a PRL-secreting pituitary tumor (MtT.W15) to young female rats. TIDA activity was determined by measuring the concentration of dopamine (DA) in pituitary stalk portal blood, the uptake and release of [3H]DA by the median eminence in vitro, and the presynaptic DA receptor activity. Eight weeks after transplantation of the tumor, serum PRL increased to approximately 100 times higher values than those in nontumor-bearing animals. Both the DA concentration and the content in pituitary stalk blood collected from rats bearing tumors for 6 weeks were significantly lower than those in nontumor-bearing rats. Injection of a DA uptake blocker, nomifensine, significantly increased stalk blood DA in nontumor-bearing rats, but did not increase DA release in tumor-bearing rats. The uptake of [3H]DA in vitro by the median eminence of rats bearing pituitary tumors for 8 weeks was lower than that in control rats. Basal and electrically induced release of [3H]DA from the median eminence in vitro from rats with tumors for 8 weeks were also significantly lower than in rats without tumors. Piribedil, a DA receptor agonist, reduced stimulated release of [3H]DA in vitro from the median eminence of rats without tumors, presumably by activating presynaptic DA receptors. However, piribedil had no effect on release of [3H]DA from the median eminence of rats with tumors. These results indicate that chronic elevation of PRL can produce a decline in TIDA function.