Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats

Uterine innervation undergoes substantial reorganization associated with ch anges in reproductive status. Nerves innervating the uterus are decreased i n pregnancy and puberty, and even the normal rodent estrous cycle is charac terized by fluctuations in numbers of myometrial nerve fibers. During the f ollicular (proestrus/estrous) phase of the estrous cycle, intact nerves are rapidly depleted and then return over the next 2-3 days in the luteal (met estrus/diestrus) phase. We hypothesize that uterine nerve depletion is init iated by increased circulating estrogen in the follicular phase. However, s tudies have not shown whether estrogen can reduce uterine innervation and, if so, whether the time course is compatible with the rapid changes observe d in the estrous cycle. These questions were addressed in the present study . Mature ovariectomized virgin rats received 17-beta -estradiol as a single injection (10 mug/kg s.c.) or chronically from timed-release pellets (0.1 mug/pellet for 3 weeks sustained release). Total (protein gene-product 9.5 -immunoreactive) and sympathetic (dopamine beta -hydroxylase- immunoreactiv e) uterine innervation was assessed quantitatively. Both total and sympathe tic innervation was abundant in uterine longitudinal smooth muscle of ovari ectomized rats. However, following acute or chronic estrogen administration , total and sympathetic fiber numbers were markedly decreased. This was not due to altered uterine size, as reductions persisted after correcting for size differences. Our results indicate that sympathetic nerves are lost fro m uterine smooth muscle after estradiol treatment in a manner similar to th at seen in the intact animal during estrus and pregnancy. This suggests tha t the rise in estradiol prior to estrus is sufficient to deplete uterine sy mpathetic innervation.