雌激素 (estrogen, E2) 是一種重要的內分泌,ㄧ般認為其影響是需要長時間且是全身性的影響。而在最近的研究指出,神經可以透過轉化脢 (aromatase) 的合成作用,增間突觸間隙區域性雌激素的濃度,使小區域中的雌激素濃度比週遭循環系統高很多,加上神經的突觸末梢已被發現含有雌激素接受器;且透過雌激素的影響,神經的構造以及傳導的效率都會改變,因此雌激素可以被當作神經傳導物質(neurotransmitter)或是神經調節物質(neuromodulator)。本篇研究主要探討雌激素 (estrogen, E2) 作為中樞神經系統的神經調節物質(neuromodulator),對脊髓之 NMDA 依賴性骨盆神經-外尿道括約肌反射之增益現象的影響。其徑可能是透過活化細胞膜與細胞內的雌激素接受器,經由不同的訊息傳導路徑,進而影響骨盆神經-尿道反射的增益現象。為觀察雌激素對骨盆經-道反射塑性的影響,我們先在麻醉鼠的骨盆經施予重複性電激 (repetitive stimulation, RS, 1Hz),以誘發骨盆經-道反射塑性之增益現象,並在 RS 達到穩定的高原期後,經由脊髓腔插管注射 E2 (single bolus, 0.1 mM),結果反射塑性的活性在給藥後有增加的趨勢 (RS:17.75±1.98 v.s. RS + E2:19.33±0.88 動作電位/電激, N=3);另外,為探討雌激素的長期效應,持續在脊髓腔內緩慢灌 E2 3 小時 (0.1ml/hr, 0.1 mM) 後,也使 RS 誘發的反射的增益現象有增加的趨勢 (RS:17.75±1.98 v.s E2+ RS 18.33 ±0.84 spikes / stimulation,P由本篇研究結果推:區域性雌激素濃度的上升的確可以使骨盆神經-尿道反射的增益現象增強。而此一反射在儲尿功能中扮演重要的角色,因此婦女在停經後缺乏雌激素的情況下,其儲尿功能或許會受到缺乏雌激素而有所影響,但詳細及確的訊息傳導徑及尿路動力學方面的影響仍需要進一步的實驗去證實。
Estrogen is a gonadal steroid with pronounced tropic effects on many diverse populations of neurons throughout the peripheral and central nervous systems.To investigate the roles of membrane and intracellular estrogen receptors on NMDA-mediated micturition functions, we characterized the effects of estrogen on the pelvic nerve -to-urethra reflex (PUR) plasticity elicited by repetitive stimulation (RS, 1 Hz) in anesthetized rats. The magnitude of the RS-induced potentiation in PUR activity was both facilitated about 5 min after E2 injection (single bolus, 0.1mM, (RS:17.75±1.98 vs. RS + E2:19.33±0.88 spikes/stimulation, N=3) and 3 hours after E2 infusion (RS:17.75±1.98 vs. E2+ RS 18.33 ±0.84 spikes / stimulation, P P<0.01 n=6). The present data suggests that estrogen modulates the spinal cord NMDA-mediated PUR plasticity in female rats and it may have different contribution to NMDA-mediated PUR plasticity between membrane and nuclear effects.Our data further suggest that alterations in neural processing within the spinal cord, mediated by estrogen.