Summary. During unilateral pregnancy in the guinea-pig there is loss of formaldehyde\x=req-\ induced fluorescence from the adrenergic nerves supplying the uterus and its vasculature. This loss occurs initially near the site of implantation at about Day 20 of gestation and spreads progressively. Implantation of wax pellets containing progesterone into the uterine lumen or the gastrocnemius muscle of virgin guinea-pigs for 7 days produced loss of fluorescence from all local adrenergic nerves. No diminution of fluorescence was seen when pellets containing oestradiol were substituted. Chronic denervation studies showed that the adrenergic axons supplying the uterus and its arteries originated from both the ovarian artery and the pelvic region. Our results suggest that loss of adrenergic fluorescence within the uterus during pregnancy is due to an effect of placental progesterone which is localized to the uterus because the high concentration of progesterone necessary to cause fluorescence loss is not attained in the systemic circulation.

1. The uterus is supplied by numerous noradrenergic sympathetic nerve fibres, which supply the intramural vasculature and also, in some species at least, the myometrium. 2. Pregnancy is associated with progressive loss of catecholamine from these nerves. Although some direct mechanical damage due to stretching of the uterine wall contributes to this effect, it is primarily due to hormonal influences. 3. In animal experiments, the changes in uterine catecholamine occurring during pregnancy are mimicked by intra-uterine administration of progesterone. 4. The action of progesterone appears not to be selective for pelvic sympathetic neurons, or those in which transmitter turnover rate is particularly slow. The mechanism of depletion is probably through inhibition of tyrosine hydroxylase activity. 5. The functional role of this phenomenon during pregnancy, if one exists, seems likely to be related to protection of the fetoplacental blood supply against sympathetically mediated vasospasm. It is also possible that circulating progesterone may have a general inhibitory action on the female sympathetic nervous system.