Effect of prolonged dopamine receptor blockade on lactotroph activity in the rat pituitary gland

The dopamine antagonist fluphenazine was administered to young rats in the presence or absence of physiological concentrations of oestradiol for periods of 230 days. An important observation arising from the investigation was that no pituitary tumours were produced by the combination of prolonged dopamine receptor blockade and small amounts of oestradiol. Prolactin (Prl) secretion increased rapidly with fluphenazine but in the absence of oestrogen lactotroph activity subsequently declined after 20 days and this decrease in hormone secretion was accompanied by a greatly increased dopamine turnover in the medio-basal hypothalamus. In contrast, small amounts of oestradiol modified the effect of fluphenazine alone causing a greatly increased secretion of Prl for a much larger period and a reduction in the dopamine content of the hypothalamus. This combination also doubled the synthesis of DNA by the pituitary compared with controls, and electron microscopy revealed evidence of increased secretory activity of the lactotrophs in the presence of both fluphenazine and oestrogen but not in those animals treated with fluphenazine only. Towards the end of the experiment Prl values declined even in the presence of oestrogen and increasing the dose of fluphenazine had no significant effect. It was suggested that eventually there may be a direct inhibitory action of the dopamine antagonist on the lactotrophs.