Expression of estrogen receptors alpha and beta by sympathetic ganglion neurons projecting to the proximal urethra of female rats.

Abstract

Urinary incontinence is prevalent in postmenopausal women and estrogen is commonly administered therapeutically. In animal models estrogen increases urethral smooth muscle agonist induced contraction but a consistent clinical benefit in humans has not been confirmed. A reason may be that estrogen affects tissues other than the urethra that are involved in continence. We determined if sympathetic nerves projecting to the urethra may also be a target for estrogen. Sympathetic neurons innervating proximal urethra smooth muscle were identified by injection of the retrograde tracer Fast Blue (Dr. Illing GmbH and Co. KG, Gross-Umstadt, Germany) in 10 ovariectomized adult female rats. Rats received a single injection of 10 microg./kg. estradiol benzoate or vehicle 24 hours before tissue harvest. Retrograde labeled sympathetic neurons expressing estrogen receptors alpha and beta in prevertebral and paravertebral ganglia were identified by immunostaining. Approximately 80% of Fast Blue labeled neurons were located in the T11 to L5 paravertebral ganglia. The remainder was located predominantly in the prevertebral suprarenal ganglia with fewer in celiac and superior mesenteric ganglia. Estrogen receptor beta was detected in more than 90% of urethra projecting neurons, while approximately 30% expressed estrogen receptor alpha. No significant change occurred after estrogen administration. Almost all examined sympathetic neurons projecting to the proximal urethra express estrogen receptor beta and a substantial subset expresses estrogen receptor alpha irrespective of estrogen titer. Therefore, estrogen may influence continence by acting not only on the urethral target, but also on its excitatory sympathetic innervation.