Aguado-Llera David, Arilla-Ferreiro Eduardo, Chowen Julie A, Argente Jesús, Puebla-Jiménez Lilian, Frago Laura M, Barrios Vicente
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Avda. Menéndez Pelayo, Madrid, Spain.
Neurobiol Aging. 2007 Sep;28(9):1396-409. doi: 10.1016/j.neurobiolaging.2006.06.009. Epub 2006 Jul 14.
Estradiol prevents amyloid-beta peptide (Abeta)-induced cell death through estrogen receptors (ERs) and modulates somatostatin (SRIF) responsiveness in the rat brain. As intracerebroventricular (ICV) Abeta25-35 administration reduces SRIFergic tone in the temporal cortex of ovariectomized (Ovx) rats, we asked whether 17beta-estradiol (E2) treatment can restore the Abeta25-35 induced changes in SRIF content, SRIF receptor density and adenylyl cyclase (AC) activity, as well as if these effects are mediated by ERs. E2 treatment did not change Abeta25-35 levels in the temporal cortex, but partially restored the SRIFergic parameters affected by Abeta insult and decreased cell death, which was correlated with Akt activation. The ER antagonist ICI 182,780 prevented the protective effect of E2 on sst2 levels, but did not modify SRIF levels. Furthermore, ICI 182,780 treatment further decreased sst2 protein and mRNA levels when administered alone to Abeta25-35-treated rats, suggesting that it may block the effects of endogenous estrogens. These findings indicate that E2 protects the temporal cortical SRIFergic system from Abeta-induced depletion independently of Abeta accumulation.
雌二醇通过雌激素受体（ERs）预防β-淀粉样肽（Aβ）诱导的细胞死亡，并调节大鼠脑中生长抑素（SRIF）的反应性。由于脑室内（ICV）注射Aβ25-35会降低去卵巢（Ovx）大鼠颞叶皮质中SRIF能神经张力，我们研究了17β-雌二醇（E2）治疗是否能恢复Aβ25-35诱导的SRIF含量、SRIF受体密度和腺苷酸环化酶（AC）活性的变化，以及这些作用是否由ERs介导。E2治疗并未改变颞叶皮质中Aβ25-35的水平，但部分恢复了受Aβ损伤影响的SRIF能参数，并减少了细胞死亡，这与Akt激活相关。ER拮抗剂ICI 182,780可预防E2对sst2水平的保护作用，但不改变SRIF水平。此外，单独给予Aβ25-35处理的大鼠ICI 182,780时，会进一步降低sst2蛋白和mRNA水平，提示其可能阻断内源性雌激素的作用。这些发现表明，E2可独立于Aβ积累保护颞叶皮质SRIF能系统免受Aβ诱导的消耗。
