Effect of catechol oestrogens on extraneuronal metabolism of noradrenaline by rabbit uterine endometrium and myometrium

Summary

The effects of 2-hydroxy and 2-methoxy oestrogens on the extraneuronal O-methylation of ³H-(−)noradrenaline were examined in progesterone-dominated, monoamine oxidase (MAO)-inhibited, rabbit uterine tissues in vitro. Both the corticosteroid- sensitive system in myometrium and the cocaine-sensitive system in endometrium were examined.

In myometrial slices preincubated with nialamide to inhibit MAO and incubated with cocaine to inhibit neuronal uptake, ³H-normetanephrine (³H-NMN) formation was inhibited in the order of potency 2-hydroxy oestrone ≥ 2-hydroxy oestradiol = 2-methoxy oestradiol ≥ 2-methoxy oestrone. In myometrial slices not exposed to cocaine and nialamide, inhibition of ³H-NMN formation by both 2-hydroxy and 2-methoxy oestradiol did not affect the formation of deaminated metabolites of ³H-(−)-noradrenaline by the alternative metabolising pathway. In endometrial slices preincubated with nialamide to inhibit MAO, only 2-hydroxy oestrogens inhibited ³H-NMN formation, but they were one to two orders of magnitude less potent in this regard than in the myometrium. The uptake of ³H-(−)-noradrenaline by MAO- and COMT-inhibited myometrial slices was inhibited by 2-hydroxy and 2-methoxy oestrogens in the order of potency 2-methoxy oestradiol ≥ 2-methoxy oestrone ≥ 2-hydroxy oestrone > 2-hydroxy oestradiol. Uptake of ³H-(−)-noradrenaline by endometrial slices was not affected by either 2-hydroxy or 2-methoxy oestrogens.

It is concluded that the O-methylatiog system for noradrenaline in myometrial tissue is more sensitive than that in endometrial tissue to the inhibitory actions of 2-hydroxy and 2-methoxy oestrogens. 2-Hydroxy oestrogens inhibit ³H-NMN formation by competing for COMT rather than noradrenaline uptake sites, since (1) they inhibited O-methylation but not uptake of ³H-noradrenaline in endometrium and (2) 2-hydroxy oestrogens were two orders of magnitude more potent against ³H-NMN formation than ³H-(−)-noradrenaline uptake in myometrium. In contrast, the ability of 2-methoxy oestrogens to inhibit myometrial but not endometrial ³H-NMN formation reflects the selective inhibitory effect of 2-methoxy oestrogens on the corticosteroid-sensitive uptake system for noradrenaline which predominates in myometrium but is minimal in endometrium. These interactions may be important in pregnancy when the local concentrations of catechol and methoxy oestrogens rise.