Role of sensory neurons to gender difference in the responses against stress.

感觉神经元通过增加胃粘膜前列环素(PGI2)水平释放降钙素基因相关肽(CGRP)，在减轻应激性胃粘膜损伤中发挥重要作用。由于雌激素增强了神经生长因子介导的感觉神经元中CGRP的产生，我们假设应激诱导的胃粘膜损伤在女性比男性发生得更少。测定了雄性和雌性野生型(CGRP+/+)小鼠、CGRP基因敲除(CGRP-/-)小鼠和Wistar大鼠应激后胃溃疡指数、胃髓过氧化物酶活性、胃组织降钙素基因相关肽及其稳定代谢产物6-酮-前列腺素F1α的含量。结果：雌性降钙素基因相关肽基因阳性小鼠胃组织中6-酮-前列腺素F1α的表达水平显著高于雄性小鼠，而胃组织中6-酮-前列腺素F1 mRNA的表达水平无性别差异。雌性大鼠胃组织中CGRP含量显著高于雄性。在大鼠中也观察到了CGRP+/+小鼠的性别差异，但这种差异可以通过香草素受体拮抗剂卡萨西平(CPZ)和雌性大鼠去卵巢(OVX)来消除。在雌二醇处理的雌性大鼠中，未观察到OVX逆转性别差异。OVX可降低雌性大鼠背根神经节神经元CGRP mRNA的表达水平，雌二醇可逆转这种降低。总之，雌激素介导的感觉神经元CGRP水平的升高可能通过减轻炎症反应而有助于减轻应激诱导的胃粘膜损伤。这可能至少部分解释了在应激诱导的啮齿类动物胃粘膜损伤的发展过程中观察到的性别差异。

Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI2). Since estrogen enhances the nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. Gastric ulcer index (UI), gastric myeloperoxidase (MPO) activity, gastric tissue levels of CGRP and 6-keto-PGF1α, a stable metabolite of PGI2, were determined in male and female wild-type (CGRP+/+) mice, CGRP knockout (CGRP-/-) mice and Wistar rats subjected to stress. Results : UI and MPO activities were lower and gastric tissue levels of 6-keto-PGF1α were higher in females than in males in CGRP+/+ mice, while there were no such gender differences in CGRP-/- mice. Gastric tissue levels of CGRP in rats were significantly higher in females than in males. Gender differences seen in CGRP+/+ mice were also observed in rats, but they were eliminated by pretreatment with capsazepine (CPZ), a vanilloid receptor antagonist, and by ovariectomy (OVX) in female rats. Reversal of gender differences by OVX was not observed in estradiol-treated female rats. Levels of CGRP mRNA in dorsal root ganglion neurons isolated from female rats were decreased by OVX and these decreases were reversed by estradiol replacement. in conclusions, estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the gender difference observed in the development of stress-induced gastric mucosal injury in rodents.