Dallman M F, Makara G B, Roberts J L, Levin N, Blum M
Endocrinology. 1985 Nov;117(5):2190-7. doi: 10.1210/endo-117-5-2190.
In the intact rat, adrenalectomy (ADX) is known to result in increased ACTH synthesis, content, and secretion from the anterior pituitary compared with those in the sham-adrenalectomized control. Treatment of adrenalectomized, rats with corticosterone prevents or reverses these changes in ACTH. Because corticosterone is known to act both at the corticotrope and at the level of CRF secretion, it is not clear to what extent the ACTH response to ADX is a result of removal of glucocorticoids from the pituitary per se. To test the role of brain input as well as the role of glucocorticoids on the corticotrope response to ADX, we performed the following experiment. Rats were prepared with anterolateral hypothalamic deafferentations (lesion) which severed CRF and arginine vasopressin cell bodies in the hypothalamus from their axonal endings in the median eminence and posterior pituitary. Control rats were subjected to sham lesions. Two days later, half of the rats in each group were subjected to either ADX or sham ADX; a subgroup of the lesioned rats was provided at the time of adrenal surgery with a constant infusion of rat CRF. Five days later, all rats were killed, and anterior pituitary levels of proopiomelanocortin (POMC) mRNA, ACTH, and protein; plasma ACTH and corticosterone, and adrenal and thymus weights were measured. In sham-lesioned rats, ADX resulted in increases in POMC mRNA, and plasma ACTH of 2.5- and 12-fold, respectively, compared to sham-adrenalectomized controls. In the absence of hypothalamic drive (lesion only), there were no responses of any of these variables to ADX. In lesioned rats driven with CRF, ADX resulted in increases in POMC mRNA and plasma ACTH of 2.2- and 2.6-fold, respectively, compared to sham ADX. After consideration of the three variables indicating ACTH synthesis, storage, and secretion and comparison of the results of ADX vs. sham ADX within and across the sets of animals, we conclude that 1) there is no autonomous response of the corticotrope to ADX; 2) the removal of corticosterone from the anterior pituitary may account for the majority of the effects of ADX on ACTH synthesis; and 3) the normal response to ADX requires secretion of CRF and increased secretion of another ACTH-releasing factor (possibly arginine vasopressin) that causes increased secretion but little synthesis of ACTH.
在完整大鼠中，已知肾上腺切除术（ADX）会导致垂体前叶促肾上腺皮质激素（ACTH）的合成、含量及分泌相较于假手术对照组有所增加。用皮质酮治疗肾上腺切除的大鼠可预防或逆转ACTH的这些变化。由于已知皮质酮会作用于促肾上腺皮质激素细胞以及促肾上腺皮质激素释放因子（CRF）分泌水平，所以尚不清楚ACTH对ADX的反应在多大程度上是由于垂体本身糖皮质激素的去除。为了测试脑输入以及糖皮质激素在促肾上腺皮质激素细胞对ADX反应中的作用，我们进行了以下实验。对大鼠进行下丘脑前外侧去传入（损伤）手术，切断下丘脑CRF和精氨酸加压素细胞体与其在正中隆起和垂体后叶的轴突末梢之间的联系。对照组大鼠进行假损伤手术。两天后，每组中的一半大鼠接受ADX或假ADX手术；在肾上腺手术时，为一组损伤大鼠持续输注大鼠CRF。五天后，处死所有大鼠，测量垂体前叶阿黑皮素原（POMC）mRNA、ACTH及蛋白质水平；血浆ACTH和皮质酮水平，以及肾上腺和胸腺重量。在假损伤大鼠中，与假肾上腺切除对照组相比，ADX导致POMC mRNA和血浆ACTH分别增加2.5倍和12倍。在没有下丘脑驱动（仅损伤）的情况下，这些变量对ADX均无反应。在用CRF驱动的损伤大鼠中，与假ADX相比，ADX导致POMC mRNA和血浆ACTH分别增加2.2倍和2.6倍。在考虑了表明ACTH合成、储存和分泌的三个变量，并比较了各组动物中ADX与假ADX的结果后，我们得出以下结论：1）促肾上腺皮质激素细胞对ADX没有自主反应；2）垂体前叶皮质酮的去除可能是ADX对ACTH合成产生大多数影响的原因；3）对ADX的正常反应需要CRF的分泌以及另一种ACTH释放因子（可能是精氨酸加压素）分泌增加，后者会导致ACTH分泌增加但合成很少。
