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Effect of ovarian steroids on the metabolism of noradrenaline in rabbit uterus

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Summary

  1. 1.

    The metabolism of (−)-3H-noradrenaline was examined in uterine slices from overiectomized rabbits which were either untreated or treated with 17β-oestradiol, alone or in combination with progesterone.

  2. 2.

    17β-oestradiol caused uterine enlargement which was not accompanied by a change in the formation per g of O-methylated metabolites (3H-NMN, 3H-VMA, 3H-MOPEG). Accumulation of unchanged 3H-noradrenaline and the formation of deaminated catechols (3H-DOMA and 3H-DOPEG) were decreased per g tissue, but increased per uterine horn.

  3. 3.

    Progesterone produced further enlargement of the oestrogen-dominated uteri which was accompanied by (a) a decrease in deaminated catechol formation and (b) an increase in 3H-NMN formation per unit mass of tissue.

  4. 4.

    In all uteri (control and hormone-treated), cocaine inhibited the formation of deaminated catechols, but not that of the O-methylated metabolites. It is suggested, therefore, that, per unit of uterine mass, the neuronal deamination of (−)-3H-noradrenaline is decreased by 17β-oestradiol and further decreased by progesterone, and that these changes reflect failure of the intraneuronal deaminating system in the whole uterus to increase in proportion to the increase in uterine mass.

  5. 5.

    Since other agents which decreased the deamination of (−)-3H-noradrenaline (cocaine and nialamide) did not affect 3H-NMN formation in oestrogen-dominated uteri, it is suggested that stimulation of 3H-NMN formation represents a direct effect of progesterone on the extraneuronal O-methylation of noradrenaline.

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Abbreviations

COMT:

Catechol-O-methyl transferase

DOCA:

deoxycorticosterone acetate

DOMA:

3,4-dihydroxy mandelic acid

DOPEG:

3,4-dihydroxyphenylethyleneglycol

MAO:

monoamine oxidase

MOPEG:

3-methoxy-4-hydroxyphenylethyleneglycol

NMN:

normetanephrine

NA+DOMA:

noradrenaline plus DOMA fraction

VMA:

vanillylmandelic acid

U-0521:

3,4-dihydroxy-2-methyl propiophenone

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Authors and Affiliations

  1. Department of Clinical and Experimental Pharmacology, University of Adelaide, 5000, Adelaide, South Australia, Australia

    J. A. Kennedy, I. S. de la Lande & R. G. Morris

Authors
  1. J. A. Kennedy
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  2. I. S. de la Lande
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  3. R. G. Morris
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Additional information

This study was supported by a grant from the National Health and Medical Research Council of Australia.

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Kennedy, J.A., de la Lande, I.S. & Morris, R.G. Effect of ovarian steroids on the metabolism of noradrenaline in rabbit uterus. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 132–142 (1984). https://doi.org/10.1007/BF00517310

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  • DOI: https://doi.org/10.1007/BF00517310

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