Ogilvie K M, Lee S, Rivier C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Brain Res. 1997 Jan 2;744(1):83-95. doi: 10.1016/s0006-8993(96)01082-7.
In male rats, lesions of the paraventricular nucleus (PVN) of the hypothalamus attenuate, but do not abolish, adrenocorticotropin (ACTH) secretion in response to acute alcohol injection. As the PVN is the major source of corticotropin-releasing factor (CRF) in the median eminence, this observation suggests that extra-PVN brain regions, and/or ACTH secretagogues other than CRF (e.g. arginine vasopressin (AVP)), mediate ACTH stimulation by alcohol. This hypothesis was tested by examining the effect of AVP immunoneutralization in PVN-lesioned (PVNx) rats. Removal of endogenous AVP diminished alcohol-evoked ACTH secretion in both sham-operated and PVNx animals, indicating that AVP from outside the PVN partially mediates the hypothalamic-pituitary-adrenal (HPA) axis response to alcohol. This led us to determine whether alcohol might also regulate AVP steady-state gene expression in the supraoptic nucleus (SON) and PVN, and/or CRF mRNA in the PVN and the central nucleus of the amygdala (AMY). In the magnocellular portion of the PVN, sham-operated animals showed significantly increased PVN levels of both CRF and AVP mRNAs 3 h after alcohol. In the SON, alcohol administration tended to decrease AVP gene expression in PVNx rats, while the drug increased AVP mRNA levels in the SON of sham-operated rats. AMY levels of CRF mRNA were unaffected by these manipulations. Finally, since the regulation of alcohol-induced AVP mRNA levels in the SON appeared to depend on the presence of the PVN, we measured peripheral levels of AVP in both sham-operated and PVNx animals after injection of vehicle or alcohol. Although AVP decreased in all groups, alcohol depressed AVP secretion to a greater extent in PVNx animals, suggesting that AVP systems are more sensitive to inhibition in the absence of the PVN. Our results demonstrate that although AVP of PVN origin may participate in regulating the stimulatory effect to AVP on ACTH secretion, AVP from areas other than the PVN also plays a role. Additionally, regulation of both AVP gene expression in the SON and secretion in the systemic circulation are altered in rats bearing lesions of the PVN.
在雄性大鼠中，下丘脑室旁核（PVN）损伤会减弱但不会消除急性酒精注射后促肾上腺皮质激素（ACTH）的分泌。由于PVN是正中隆起中促肾上腺皮质激素释放因子（CRF）的主要来源，这一观察结果表明，PVN以外的脑区和/或CRF以外的ACTH促分泌素（如精氨酸加压素（AVP））介导了酒精对ACTH的刺激作用。通过检测AVP免疫中和对PVN损伤（PVNx）大鼠的影响来验证这一假设。去除内源性AVP可减少假手术组和PVNx组动物酒精诱发的ACTH分泌，表明来自PVN以外的AVP部分介导了下丘脑-垂体-肾上腺（HPA）轴对酒精的反应。这促使我们确定酒精是否也可能调节视上核（SON）和PVN中AVP的稳态基因表达，以及PVN和杏仁核中央核（AMY）中CRF mRNA的表达。在PVN的大细胞部分，假手术组动物在酒精注射3小时后PVN中CRF和AVP mRNA水平均显著升高。在SON中，给予酒精倾向于降低PVNx大鼠中AVP基因表达，而该药物可增加假手术组大鼠SON中AVP mRNA水平。这些操作对AMY中CRF mRNA水平没有影响。最后，由于SON中酒精诱导的AVP mRNA水平的调节似乎依赖于PVN的存在，我们在注射溶剂或酒精后测量了假手术组和PVNx组动物外周血中AVP的水平。尽管所有组中AVP均下降，但酒精对PVNx组动物AVP分泌的抑制作用更大，这表明在没有PVN的情况下，AVP系统对抑制作用更敏感。我们的结果表明，尽管来自PVN的AVP可能参与调节AVP对ACTH分泌的刺激作用，但来自PVN以外区域的AVP也发挥作用。此外，PVN损伤的大鼠中SON中AVP基因表达和全身循环中AVP分泌的调节均发生改变。
