Changes in the Function of Tuberoinfundibular Dopaminergic Neurons after Long-Term Estradiol Treatment in Fischer 344 Rats

Abstract

The functions of tuberoinfundibular dopaminergic (ΗDA) neurons after long-term estradiol treatment were investigated in Fischer 344 (F344) rats which have high susceptibility to estradiol-induced prolactin (PRL)-secreting pituitary tumors. Dopamine synthesis in and release from TTDA neurons were determined in vitro by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence following incubation with a DOPA decarboxylase inhibitor and endogenous dopamine release from the median eminence, respectively. The concentration of serum PRL and the weight of the anterior pituitary in ovariectomized F344 rats were markedly increased 3 weeks after a single injecction of 2 mg estradiol valerate (EV) and decreased thereafter, but still showed higher levels at 15 and 24 weeks than control ovariectomized rats. Dopamine contents in the median eminence were decreased 3 weeks and unchanged 24 weeks after EV treatment. DOPA accumulation and basal dopamine release in the median eminence of F344 rats were decreased 3 weeks and increased 15 and 24 weeks after EV treatment, similarly to those of Wistar rats as reported previously. However, EV treatment, which caused similar increases in the concentrations of serum PRL and estradiol in F344 and Wistar rats, decreased KCl-induced dopamine release in Wistar rats at 3 weeks, but failed to do so in F344 rats. KC1-induced dopamine release 24 weeks after a single EV injection in F344 rats was greater than that in control rats, whereas the dopamine release 24 weeks after the last treatment of 4 injections at 3-week intervals was not different from that in control rats. Sustained high levels of serum PRL for 3 weeks achieved by pituitary transplants under the kidney capsule increased basal and KCl-induced dopamine release in F344 rats. These results suggest that (1) estradiol is less effective in inhibiting KCl-induced release of dopamine from ΗDA neurons in F344 rats, and (2) extension of the period of estradiol treatment suppresses the enhancement of ΗDA function by estradiol withdrawal.

Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage

“…injection of estradiol valerate to OVX animals markedly increased, after 3 weeks, serum PRL levels and pituitary weight and reduced DA content in the ME. Twenty-four weeks after estrogen administration, PRL levels and pituitary weight had decreased but were still above control values whereas ME DA content had returned to pre-injection levels [1]. These two reports are in general agreement with the present data.…”