Veldhuis H D, De Kloet E R
Neuroendocrinology. 1982;34(5):374-80. doi: 10.1159/000123331.
The effect of hypophysectomy on the number of corticosterone receptor sites was investigated in three rat brain regions and was compared with the effect of long-term adrenalectomy. Subsequently, the effect on receptor capacity was measured after the hypophysectomized rats had received as substitution therapy ACTH1-24 and smaller peptide fragments lacking corticotropic activity. All rats (sham and hypophysectomy) were adrenalectomized 24 h prior to sacrifice for depletion of endogenous adrenal hormones and replacement therapy was discontinued at that time. Extensive perfusion with saline was carried out at the time of sacrifice. 3H-corticosterone binding was measured in cytosol by means of an in vitro assay. 2 weeks after hypophysectomy, the apparent maximal binding capacity (Bmax) of the corticosterone receptor system was increased by 60, 36 and 72% in hippocampus, hypothalamus and septum, respectively. The increase in Bmax in the hippocampus of hypophysectomized rats was 30% higher than the increase in animals adrenalectomized 2 weeks previously. Replacement with ACTH1-24 markedly decreased the binding capacity in all brain regions investigated. Replacement with the behaviorally active ACTH4-10 sequence reduced the number of corticosterone receptor sites in the hippocampus by 21%, while the behaviorally inactive ACTH11-24 sequence was ineffective. Des-glycinamide-arginine-vasopressin was also ineffective. There were no alterations in binding affinity for corticosterone in hippocampal cytosol after the surgical procedures or after the different replacement therapies. It is concluded that the neurotropic ACTH4-10 sequence reduces the number of corticosterone receptor sites in the hippocampus of the hypophysectomized rat. The action of ACTH4-10 was specific for the hippocampus and was not observed in other brain regions or plasma transcortin.
研究了垂体切除对大鼠三个脑区皮质酮受体位点数量的影响，并与长期肾上腺切除的影响进行了比较。随后，在垂体切除的大鼠接受促肾上腺皮质激素1 - 24（ACTH1 - 24）和缺乏促肾上腺皮质激素活性的较小肽片段作为替代疗法后，测量了对受体容量的影响。所有大鼠（假手术组和垂体切除组）在处死前24小时进行肾上腺切除，以耗尽内源性肾上腺激素，此时替代疗法停止。处死时用生理盐水进行广泛灌注。通过体外测定法测量细胞溶质中3H - 皮质酮的结合。垂体切除2周后，海马、下丘脑和隔区皮质酮受体系统的表观最大结合容量（Bmax）分别增加了60%、36%和72%。垂体切除大鼠海马中Bmax的增加比2周前肾上腺切除的动物高30%。用ACTH1 - 24替代显著降低了所有研究脑区的结合容量。用具有行为活性的ACTH4 - 10序列替代使海马中皮质酮受体位点数量减少了21%，而无行为活性的ACTH11 - 24序列无效。去甘氨酰胺 - 精氨酸 - 加压素也无效。手术操作或不同替代疗法后，海马细胞溶质中对皮质酮的结合亲和力没有改变。结论是，具有神经趋向性的ACTH4 - 10序列减少了垂体切除大鼠海马中皮质酮受体位点的数量。ACTH4 - 10的作用对海马具有特异性，在其他脑区或血浆转皮质素中未观察到。
