Lutz-Bucher B, Kovacs K, Makara G, Stark E, Koch B
Neuroendocrinology. 1986;43(5):618-24. doi: 10.1159/000124590.
The regulation of pituitary vasopressin (VP) receptor concentration was investigated in rats with antero-lateral cuts (ALC) placed around the hypothalamus, as well as in Brattleboro homozygotes (HO) that genetically suffer from a lack of AVP. Hypothalamic ALCs caused a reduction in (3H)-AVP binding, while counteracting the dramatic fall in binding that normally occurs after adrenalectomy. Surprisingly, in HO rats, long-term adrenalectomy did cause pituitary AVP receptor number to decrease to an extent similar to that seen in normal rats. However, the receptor disappeared twice as rapidly in heterozygote controls than in HO animals, with calculated half-lives of 1.1 and 2.0 days, respectively. In HO, chronic administration of VP reduced receptor concentration by about 80%, while the same dose of oxytocin (OT) produced only a 20-30% reduction. Whereas dexamethasone injections did reverse the depressing effect of adrenalectomy on pituitary AVP receptors, they failed to enhance binding in sham-operated controls, treated or not with VP; thereby suggesting a central site of action of the steroid. In contrast, in rats with hypothalamic ALCs (i.e. with the pituitary lacking central control), corticosterone implants did antagonize the reduction in receptor density caused by adrenalectomy. We conclude that the pituitary AVP receptor system lies mainly under control of the central nervous system, through a mechanism of action that not only seems to imply AVP and OT, but probably also some other hypothalamic factor(s). Glucocorticoids appear to exert a dual effect, acting indirectly through negative feedback control of neuropeptide release and, possibly, also directly on the pituitary to regulate binding sites.
研究了下丘脑周围进行前外侧切割（ALC）的大鼠以及遗传性缺乏抗利尿激素（AVP）的布拉德福德纯合子（HO）中垂体血管加压素（VP）受体浓度的调节情况。下丘脑ALC导致（3H）-AVP结合减少，同时抵消了肾上腺切除术后通常出现的结合急剧下降。令人惊讶的是，在HO大鼠中，长期肾上腺切除术确实导致垂体AVP受体数量减少到与正常大鼠相似的程度。然而，杂合子对照组中受体消失的速度是HO动物的两倍，计算出的半衰期分别为1.1天和2.0天。在HO中，慢性给予VP可使受体浓度降低约80%，而相同剂量的催产素（OT）仅使受体浓度降低20 - 30%。地塞米松注射确实逆转了肾上腺切除术对垂体AVP受体的抑制作用，但在假手术对照组中，无论是否用VP处理，地塞米松都未能增强结合；这表明该类固醇的作用位点在中枢。相比之下，在进行下丘脑ALC的大鼠中（即垂体缺乏中枢控制），皮质酮植入物确实拮抗了肾上腺切除术引起的受体密度降低。我们得出结论，垂体AVP受体系统主要受中枢神经系统控制，其作用机制似乎不仅涉及AVP和OT，还可能涉及其他一些下丘脑因子。糖皮质激素似乎发挥双重作用，通过对神经肽释放的负反馈控制间接起作用，也可能直接作用于垂体以调节结合位点。
