Romeo Russell D, Lee Susan J, McEwen Bruce S
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.
Neuroendocrinology. 2004;80(6):387-93. doi: 10.1159/000084203. Epub 2005 Feb 28.
The pubertal development of the hypothalamic-pituitary-adrenal (HPA) axis has received relatively little experimental attention. As puberty is marked by an increase in the susceptibility to various psychiatric disorders that may be related to HPA dysfunction, it is imperative to elucidate the pubertal development of this neuroendocrine axis. To date, the limited research in this area has been conducted primarily on males. Presently, we investigated stress responsiveness, as measured by both stress hormones (e.g., corticotropin (ACTH) and corticosterone) and gonadal steroids, in intact and ovariectomized prepubertal and adult female rats before and after a 30-min session of restraint stress. We report here that intact prepubertal females exhibit an extended corticosterone stress response (30-45 min longer) compared to intact adults. Moreover, ovariectomized prepubertal females continue to exhibit a prolonged stress-induced corticosterone and progesterone response compared to ovariectomized adults, indicating these protracted responses prior to puberty are independent of ovarian hormones. ACTH levels were not significantly different between intact and ovariectomized prepubertal and adult animals at all the post-stress time points measured, suggesting that the prolonged corticosterone response in prepubertal females is due to an enhanced sensitivity to ACTH at the level of the adrenal cortex. Taken together, these data indicate that stress reactivity changes dramatically during puberty in females. Furthermore, these data demonstrate additional development of the HPA axis during pubertal maturation, resulting in a more quickly terminated stress response in adulthood.
下丘脑 - 垂体 - 肾上腺(HPA)轴的青春期发育受到的实验关注相对较少。由于青春期的特征是对各种可能与HPA功能障碍有关的精神疾病的易感性增加,因此阐明这个神经内分泌轴的青春期发育势在必行。迄今为止,该领域有限的研究主要是在雄性动物身上进行的。目前,我们在30分钟的束缚应激前后,研究了完整和去卵巢的青春期前及成年雌性大鼠的应激反应性,通过应激激素(如促肾上腺皮质激素(ACTH)和皮质酮)以及性腺类固醇来衡量。我们在此报告,与完整的成年雌性大鼠相比,完整的青春期前雌性大鼠表现出延长的皮质酮应激反应(长30 - 45分钟)。此外,与去卵巢的成年雌性大鼠相比,去卵巢的青春期前雌性大鼠继续表现出应激诱导的皮质酮和孕酮反应延长,表明青春期前的这些延长反应独立于卵巢激素。在所有测量的应激后时间点,完整和去卵巢的青春期前及成年动物的ACTH水平没有显著差异,这表明青春期前雌性大鼠皮质酮反应延长是由于肾上腺皮质水平对ACTH的敏感性增强。综上所述,这些数据表明雌性在青春期期间应激反应性发生了显著变化。此外,这些数据证明了青春期成熟过程中HPA轴的进一步发育,导致成年期应激反应更快终止。