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.
D000077584:2-Methoxyestradiol; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002369:Castration; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008745:Methylation; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004958:Estradiol; D000077584:2-Methoxyestradiol; D007986:Luteinizing Hormone; C001390:2-hydroxyestradiol; D009638:Norepinephrine