Shanks N, McCormick C M, Meaney M J
Department of Psychiatry, Douglas Hospital Research Centre, McGill University, Quebec, Canada.
Brain Res Dev Brain Res. 1994 Jun 17;79(2):260-6. doi: 10.1016/0165-3806(94)90130-9.
Exposure to endotoxin is known to activate hypothalamic-pituitary-adrenal (HPA) responses in both adult and neonatal animals. We have previously reported that female rat pups exhibit greater HPA responses to endotoxin challenge than males. It is unclear, however, whether observed gender differences at this early age are mediated by gonadal factors. In the present investigation we assessed the effects of neonatal gonadectomy on HPA responses to endotoxin challenge in the developing rat. On the first day of life Long-Evans rat pups were gonadectomized or subjected to sham surgery. On the third day of life the pups were injected i.p. with 0.05 mg/kg Salmonella enteritidis endotoxin. Four hours following injection, trunk blood and tissues were collected for determination of plasma hormones and median eminence corticotropin-releasing hormone (CRH) content. Intact female rat pups were found to exhibit greater plasma adrenocorticotrophic hormone (ACTH) and corticosterone responses to endotoxin challenge compared with male animals. Plasma corticosterone levels, both total and free steroid, were markedly altered by removal of gonads such that responding to endotoxin was elevated in males, while it was reduced in females. In contrast, ACTH responding in male pups was not altered following gonadectomy, whereas female ACTH responses were significantly reduced compared with endotoxin-treated intact controls. CRH levels in the median eminence were reduced following endotoxin challenge to an equivalent extent in both male and female pups and this effect was partially attenuated by the removal of gonadal hormones. These data suggest that sex differences in HPA responses to immune challenge may be mediated at different levels of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)
已知接触内毒素会激活成年和新生动物的下丘脑-垂体-肾上腺（HPA）反应。我们之前报道过，雌性幼鼠对内毒素刺激的HPA反应比雄性幼鼠更强。然而，目前尚不清楚这种早期观察到的性别差异是否由性腺因素介导。在本研究中，我们评估了新生期去势对发育中大鼠HPA对内毒素刺激反应的影响。出生第一天，将Long-Evans幼鼠去势或进行假手术。出生第三天，给幼鼠腹腔注射0.05 mg/kg肠炎沙门氏菌内毒素。注射后4小时，采集躯干血液和组织以测定血浆激素和正中隆起促肾上腺皮质激素释放激素（CRH）含量。发现完整的雌性幼鼠对内毒素刺激的血浆促肾上腺皮质激素（ACTH）和皮质酮反应比雄性动物更强。去除性腺后，血浆皮质酮水平（包括总类固醇和游离类固醇）发生显著变化，使得雄性对内毒素的反应升高，而雌性则降低。相比之下，去势后雄性幼鼠的ACTH反应未改变，而雌性ACTH反应与经内毒素处理的完整对照组相比显著降低。内毒素刺激后，雄性和雌性幼鼠正中隆起的CRH水平均同等程度降低，去除性腺激素可部分减弱这种效应。这些数据表明，HPA对免疫刺激反应的性别差异可能在HPA轴的不同水平介导。（摘要截短于250字）
