Oestrogen-induced hyperprolactinaemia in the rat: reduced concentrations of hypothalamic dopamine and the effects of bromocriptine.

The induction of hyperprolactinaemia in the male rat following chronic oestrogen administration over 3 months was shown to result in a highly significant reduction in hypothalamic dopamine (DA) concentration as well as significant reductions in hypothalamic noradrenaline (NA) and serotonin (5-HT). Significant increases in hypothalamic DA synthesis were found 4 days after a single dose of oestrogen but not after 3 months' chronic treatment. However, after the latter treatment there was a reduction in the ratio of the level of DA to its acidic metabolites in the hypothalami of the rats. When small doses of the ergot bromocriptlne were chronically administered to oestrogen-treated rats a significant return towards normal concentrations was noted for serum prolactin and the hypo-thalamic catecholamines but 5-HT was suppressed even further. An acute dose of bromocriptine given to rats which had been chronically administered oestrogen caused a complete reversal of hyper-prolactinaemia and a small increase in hypothalamic DA levels. The suppressive effects of chronic oestrogen treatment on hypothalamic monoamines in intact rats was not observed in hypophysectomized rats. In hypophysectomized rats after chronic oestrogen treatment hypothalamic DA concentration was not significantly different from that of normal controls while both NA and 5-HT were significantly elevated. In this investigation oestrogen-induced hyperprolactinaemia was found to relate to hypothalamic DA but not to NA or 5-HT. In normal and oestrogen-treated rats there was found to ,be a highly significant correlation between serum prolactin and hypothalamic DA concentration. The data indicate that the reduction in hypothalamic DA is primarily due to the hyperprolactinaemia and not to a direct action of oestrogen on the brain. This study raises the possibility that reduced hypothalamic DA concentrations may be related to the degenerative hypothalamic lesions seen in chronically oestrogen-treated rats and that these lesions may be an effect of prolactin rather than oestrogen as proposed previously.