Effects of chronic and acute oestrogen treatment on the developing noradrenaline‐containing nerves of the rat uterus

Abstract

The developing noradrenaline-containing (NA-C) sympathetic nerves of the rat uterus were analyzed following acute and chronic treatment with oestrogen. Histochemical methods were used in association with nerve density measurements and biochemical assays. For comparative purposes, noradrenaline (NA) levels were measured in the urinary bladder and right auricle following chronic oestrogen treatment. Acute treatment was performed by s.c. administration of a single dose of 40 micrograms oestradiol cypionate on the 25th day of age. Chronic treatment consisted of four doses of 10 micrograms oestradiol on days 10, 15, 20 and 25 of postnatal development. Both acute- and chronic-treated animals were killed at 28 days of age. The main biochemical findings were the following: (a) both acute and chronic oestrogen treatment increased the weight of the uterine horn, parametrial tissue and uterine cervix; (b) in the uterine horn, the total content of NA was reduced following both oestrogen treatments. However, the degree of reduction was greater after chronic treatment; (c) in the parametrial tissue, the NA levels were reduced only after chronic treatment; (d) in the cervix, the NA total content was increased after both treatments; (e) in the urinary bladder, there was a parallel increase between organ growth and NA content following chronic oestrogen treatment; (e) in the auricle neither the tissue weight nor the total content of NA were changed by chronic estrogen treatment. Histochemical studies showed that: (a) acute treatment with one single dose of oestradiol, provoked a marked reduction in the density of NA-C nerves associated with the myometrial and parametrial smooth muscle, without affecting the innervation of blood vessels; (b) following chronic treatment, the only fibers we were able to recognize were those associated with blood vessels. These fibers were thinner and less intensely fluorescent than in controls. Results are interpreted considering the differential sensitivity of uterine nerves to sex hormones. A possible involvement of oestrogen in changes of noradrenergic innervation of the uterus following puberty is discussed.

Effects of Infantile/Prepubertal Chronic Estrogen Treatment and Chemical Sympathectomy with Guanethidine on Developing Cholinergic Nerves of the Rat Uterus

“…Considering that the reduced intercept density of these nerve fibers did not persist after correction for changes in the target, it might be suggested that estrogen provoked the "dilution" of those cholinergic fibers by its hypertrophic effects on the myometrium. Dilution of the sympathetic myometrial nerve fibers that fail to keep pace with the size of the uterus was also seen in the rat during puberty (Brauer et al 1992) and after acute (Brauer et al 1995) and chronic exposure to estrogen of young adult rats (Chávez-Genaro et al, In press). This unusual behavior of uterine sympathetic nerves clearly contrasts with the responses of similar nerves in other hypertrophic target tissues, including muscular visceral organs, in which changes in target size induce coordinated changes in their innervating neurons (Gabella 1984;Steers et al 1990).…”

“…The intercept density of nerve bundles and myometrial nerve fibers was estimated directly under the microscope using a 1-mm-long ocular scale set perpendicular to the uterine long axis and a ϫ 10 objective lens (Brauer et al 1992(Brauer et al ,1995. This orientation of the counting line ensured a comparable sampling because most of the non-vascular nerve fibers in the longitudinal myometrial layer run parallel to the uterine long axis.…”

“…Control animals from matched litters were injected with 0.1 ml of peanut oil per dose. All animal groups were sacrificed at 28 days of age (Brauer et al 1995(Brauer et al ,1999.…”

“…loss of norepinephrine histofluorescent-labeled sympathetic nerves and reduces by 80% the total content of norepinephrine (NE) in the uterine horn (Brauer et al 1995(Brauer et al ,1999. It is not known, however, whether chronic exposure to estrogen affects the development of uterine cholinergic nerves.…”

Distributions of estrogen receptors alpha and beta in sympathetic neurons of female rats: Enriched expression by uterine innervation

“…This is due to actual degeneration of sympathetic terminal branches as confirmed using the pan-neuronal marker PGP 9.5 and by electron microscopic analysis (Sporrong et al, 1978;Haase et al, 1997;Brauer and Burnstock, 1998;Zoubina and Smith, 2000). Evidence that these degenerative changes are induced by estrogen comes from findings that acute or chronic administration of estrogen to ovariectomized (OVX) rats or mice results in rapid and robust loss of uterine sympathetic nerve terminals (Brauer et al, 1995; and that mice in which the estrogen receptor ␣ has been rendered nonfunctional show dramatic increases in sympathetic innervation . Circulating estrogen therefore exerts powerful effects on the status of uterine sympathetic innervation.…”