Effect of progesterone on the metabolism of noradrenaline in rabbit uterine endometrium and myometrium.
The metabolism of (-)-3H-noradrenaline was examined in the endometrium and the myometrium from rabbits which had received 17 beta-oestradiol, either alone (oestrogen-dominated) or with progesterone (progesterone-dominated). The progesterone treatment resulted in a 2.5-fold increase in 3H-NMN formation in the endometrium, with no change in 3H-DOPEG, 3H-DOMA or 3H-OMDA formation. In the myometrium, progesterone caused a 5-fold increase in 3H-NMN formation and a 2.5-fold increase in 3H-OMDA formation, but did not affect 3H-DOPEG or 3H-DOMA formation. In the progesterone-dominated endometrium, both 3H-NMN and 3H-OMDA formation were strongly inhibited by cocaine 30 mumol/l. When O-methylation was inhibited by a COMT inhibitor, cocaine prevented the resultant increases in deamination of noradrenaline to 3H-DOPEG and in the accumulation of 3H-noradrenaline by the tissue. The 3H-noradrenaline which accumulated in endometria, in which both MAO and COMT were inhibited, was firmly bound; desipramine 3 mumol/l and (+)-amphetamine 10 mumol/l were equieffective with cocaine 30 mumol/l in inhibiting the accumulation. Cocaine 30 mumol/l was without effect on 3H-NMN and 3H-OMDA formation in the progesterone-dominated myometrium, nor did it prevent the increase in 3H-DOPEG formation produced by COMT inhibition. Fluorescent histochemical analysis of the endometrium indicated that the epithelial cells of the endometrial glands were the site of cocaine-sensitive noradrenaline accumulation. It is concluded that progesterone stimulates O-methylation in the endometrium and myometrium in different ways.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D011817:Rabbits; D014018:Tissue Distribution
D011374:Progesterone; D004958:Estradiol; D002394:Catechol O-Methyltransferase; D003042:Cocaine; D007545:Isoproterenol; D009638:Norepinephrine