Estrogen Promotes Sympathetic Nerve Regeneration in Rat Proximal Urethra

ObjectivesTo assess whether sympathetic reinnervation of the rat proximal urethra is affected by differences in estrogen levels. Sympathetic innervation mediates tonic contraction of proximal urethral smooth muscle, thus contributing to urinary continence. Urethral innervation is particularly susceptible to damage during vaginal delivery, a time characterized by decreasing estrogen levels.MethodsAdult female rats were ovariectomized and implanted with pellets containing vehicle or estrogen to achieve serum levels similar to rodent pregnancy. The rats were injected intravenously with vehicle or the selective sympathetic neurotoxin 6-hydroxydopamine, which produces uniform and complete destruction of terminal sympathetic axons. At 1, 4, 12, and 25 days, tyrosine hydroxylase-immunoreactive sympathetic innervation of the proximal urethral smooth muscle was assessed quantitatively.ResultsIn rats with intact innervation, the proximal urethra is densely innervated, and nerve density is comparable, irrespective of estrogen status. 6-Hydroxydopamine induced marked sympathetic axon disruption by day 1 and complete denervation by 4 days after injection in the ovariectomized rats receiving vehicle or estrogen. In the vehicle-treated rats, few nerves were present at 12 days after sympathectomy, and innervation remained substantially less than normal levels at 25 days. In estrogen-treated rats, sympathetic reinnervation was twofold greater at 12 days and by 25 days was comparable to that of the controls.ConclusionsEstrogen improves sympathetic reinnervation of the proximal urethra. Estrogen titers in individuals with urethral sympathetic nerve damage might, therefore, influence the rate and extent of urethral smooth muscle reinnervation.