Enhanced dopamine synthesis and release in vitro in the median eminence of rat hypothalamus are associated with involution of estradiol-induced pituitary tumors.

Changes in the functions of tuberoinfundibular dopaminergic (TIDA) neurons were investigated during the period when the involution of estradiol-induced PRL-secreting pituitary tumors was occurring. Dopamine synthesis and release in vitro by TIDA neurons were determined by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence and endogenous dopamine release from the median eminence, respectively. Three weeks after a single injection of 2 mg estradiol valerate into ovariectomized rats, there was a marked increase in the weight of anterior pituitaries and the concentration of serum PRL, but a decrease in K+-induced DOPA accumulation in vitro in the median eminence. Twelve weeks after estradiol treatment, by which time pituitary weights and PRL concentrations declined considerably, K+-induced DOPA accumulation in the median eminence rose 5-fold compared to that in control animals. This change in DOPA accumulation persisted for 24 weeks. Increases were observed at 12 weeks in K+-induced as well as basal and (Bu)2cAMP-induced DOPA accumulation in the median eminence. The increases in basal and (Bu2cAMP-induced DOPA accumulation were not altered by Ca2+ removal from medium. In parallel to the changes in DOPA accumulation, basal and K+-induced release in vitro of dopamine from the median eminence into the medium were decreased 3 weeks after estradiol treatment, but increased at 12 and, in part, 24 weeks. The increases in basal and K+-induced dopamine release were observed even after Ca2+ removal from medium. These results suggest that basal, extracellular Ca2+-dependent, and cAMP-dependent dopamine synthesis as well as basal and depolarization-induced dopamine release in TIDA neurons are stimulated during the period of involution of pituitary tumors associated with estradiol withdrawal.