Harrelson A L, McEwen B S
J Neurosci. 1987 Sep;7(9):2807-10. doi: 10.1523/JNEUROSCI.07-09-02807.1987.
In investigating the feedback effects of circulating hormones on the brain, we showed previously that adrenalectomy (ADX) increases vasoactive intestinal peptide (VIP)-stimulated cAMP generation in slices from rat hippocampus, a brain structure with high levels of glucocorticoid receptors. This effect is reversed by replacement with glucocorticoids such as dexamethasone (DEX) and corticosterone (CORT). Here we report that, like ADX, hypophysectomy (HYPOX) also elevates VIP-stimulated cAMP generation, compared with sham-operated controls. Moreover, like glucocorticoid replacement, administration of ACTH to HYPOX rats causes a decrease in cAMP stimulation by VIP. Furthermore, ACTH had no effect when given to HYPOX + ADX rats, indicating that the effects of ACTH require the presence of adrenal steroid secretion. However, we find that ACTH may have a permissive role in this glucocorticoid effect because, in the absence of the pituitary, DEX treatment does not decrease VIP-stimulated cAMP levels in the hippocampus. In addition, hippocampal beta-adrenergic-stimulated cAMP accumulation was not suppressed by DEX treatment of HYPOX rats, which again is different from the effect of DEX treatment on ADX animals. These results are discussed in terms of possible synergism between pituitary hormones and steroid hormones in exerting feedback actions on brain function.
在研究循环激素对大脑的反馈作用时，我们先前发现，肾上腺切除术（ADX）可增加血管活性肠肽（VIP）刺激的大鼠海马体切片中的环磷酸腺苷（cAMP）生成，海马体是一种糖皮质激素受体水平较高的脑结构。用诸如地塞米松（DEX）和皮质酮（CORT）等糖皮质激素替代可逆转这种作用。在此我们报告，与假手术对照组相比，垂体切除术（HYPOX）同样会提高VIP刺激的cAMP生成，这与ADX的情况类似。此外，与糖皮质激素替代一样，给垂体切除大鼠注射促肾上腺皮质激素（ACTH）会导致VIP对cAMP的刺激作用减弱。此外，给垂体切除 + 肾上腺切除大鼠注射ACTH没有效果，这表明ACTH的作用需要肾上腺类固醇分泌的存在。然而，我们发现ACTH可能在这种糖皮质激素作用中具有允许作用，因为在没有垂体的情况下，DEX治疗不会降低海马体中VIP刺激的cAMP水平。此外，DEX治疗垂体切除大鼠并没有抑制海马体中β-肾上腺素能刺激的cAMP积累，这再次与DEX治疗对肾上腺切除动物的作用不同。我们从垂体激素和类固醇激素在对脑功能发挥反馈作用时可能存在的协同作用方面讨论了这些结果。
