Effect of 2-substituted oestrogens in vivo on the metabolism of noradrenaline in rat brain.

The effects of oestradiol-17 beta, 2-hydroxyoestradiol-17 beta and 2-methoxyoestradiol-17 beta on the metabolism of [3H]noradrenaline were studied in various brain regions of ovariectomized in rats in vivo. Under the experimental conditions chosen, oestradiol-17 beta had no effect on the metabolic pattern of noradrenaline. After pre-treatment of ovariectomized rats with 2-hydroxyoestradiol-17 beta, the formation of methylate metabolites of noradrenaline (normetanephrine and 3-methoxy-4-hydroxyphenylglycol sulphate) was reduced, whereas that of non-methylated products (3,4-dihydroxymandelic acid and 3,4-dihydroxyphenylglycol sulphate) was increased. The inhibition of methylation was most pronounced in posterior hypothalamus and less significant in anterior hypothalamus and thalamus. Pre-treatment with 2-methoxyoestradiol-17 beta yielded inconsistent results. From the findings described here it may be concluded that 2-hydroxyoestradiol-17 beta, as previously shown in vitro, also affects the metabolism of noradrenaline in vivo by directly interacting with the catechol-O-methyltransferase. It is suggested that this metabolic effect may be responsible - at least to some extent - for the inhibitory effect of 2-hydroxyoestradiol-17 beta on LH secretion.