Locatelli V, Cella S G, Loche S, Pintor C, Müller E E
Life Sci. 1984 Nov 5;35(19):1989-95. doi: 10.1016/0024-3205(84)90480-6.
We have investigated the effect of hypothalamo-pituitary disconnection in the rat on the growth hormone (GH) responsiveness to human pancreatic GH-releasing factor (hpGRF). Adult female rats, sham-operated (sham-op) or bearing a complete mechanical ablation of the mediobasal hypothalamus (MBH-A) were challenged, while under urethane anesthesia, with hpGRF-40 (20,100,500 ng/rat i.v.) at different time intervals after surgery. In sham-op rats only 500 ng/rat of hpGRF-40 stimulated GH release, while in 1-and 7-day MBH-A rats the stimulation also occurred with the lower hpGRF doses and the rise in plasma GH was greater than in sham-op controls. Twenty-one and 42 days after the placing of the lesions the GH response to hpGRF-40 was still present at the 500 ng/rat dose, though it was smaller than in sham-op controls. Evaluation of pituitary GH content demonstrated a progressive and rapid decline starting the first day after the placing of the lesions. These data indicate that GH responsiveness to hpGRF is: enhanced in the anterior pituitary shortly after hypothalamo-pituitary disconnection and, despite a striking reduction of the pituitary GH stores, it is maintained after these lesions. The physiologic growth hormone (GH) releaser in the rat is GH-releasing factor and, recently, a group of peptides has been characterized from human pancreatic tumors (hpGRFs) (1,2) which are potent and specific GH-releasers in both animals and man. The availability of these peptides, which show a high degree of homology with the physiologic rat hypothalamic GRF, offers the unique opportunity to assess somatotrope responsiveness to GRF molecules in rats with hypothalamo-pituitary disconnection. In this study we have first evaluated the GH pituitary responsiveness to increasing doses of hpGRF-40 in rats following mechanical ablation of the medio-basal hypothalamus. These rats, by definition, lack the effect of both central nervous system (CNS) inhibitory (e.g. somatostatin) and stimulatory (e.g. GRF) influences to GH release. With the aim to ascertain how the lack of these two opposing inputs reflects on the secretory capacity of the somatotropes, we also investigated the GH response to hpGRF-40 at different time intervals after the lesioning. In a study in rats with electrolytic lesions of the ventromedial-arcuate region of the hypothalamus Tannenbaum et al had shown persistence of the GH response to huge doses of a hpGRF analog.
我们研究了大鼠下丘脑 - 垂体分离对生长激素（GH）对人胰腺生长激素释放因子（hpGRF）反应性的影响。成年雌性大鼠，进行假手术（假手术组）或完全机械性切除中基底部下丘脑（MBH - A），在乌拉坦麻醉下，于术后不同时间间隔用hpGRF - 40（20、100、500 ng/大鼠，静脉注射）进行刺激。在假手术组大鼠中，仅500 ng/大鼠的hpGRF - 40能刺激GH释放，而在MBH - A术后1天和7天的大鼠中，较低剂量的hpGRF也能产生刺激作用，且血浆GH的升高幅度大于假手术对照组。在损伤后21天和42天，对500 ng/大鼠剂量的hpGRF - 40仍有GH反应，尽管比假手术对照组小。垂体GH含量评估显示，在损伤后第一天就开始出现进行性快速下降。这些数据表明，GH对hpGRF的反应性在垂体 - 下丘脑分离后不久的垂体前叶中增强，并且尽管垂体GH储备显著减少，但在这些损伤后仍得以维持。大鼠体内生理性的生长激素（GH）释放因子是生长激素释放因子，最近，从人胰腺肿瘤中鉴定出一组肽（hpGRFs）（1,2），它们在动物和人类中都是强效且特异性的GH释放因子。这些肽与生理性大鼠下丘脑GRF具有高度同源性，它们的可得性为评估下丘脑 - 垂体分离大鼠中生长激素细胞对GRF分子的反应性提供了独特的机会。在本研究中，我们首先评估了在中基底部下丘脑机械性切除后的大鼠中，垂体对递增剂量hpGRF - 40的GH反应性。根据定义，这些大鼠缺乏中枢神经系统（CNS）对GH释放的抑制（如生长抑素）和刺激（如GRF）影响。为了确定这两种相反输入的缺乏如何反映在生长激素细胞的分泌能力上，我们还研究了损伤后不同时间间隔对hpGRF - 40的GH反应。在一项对下丘脑腹内侧 - 弓状区域进行电解损伤的大鼠研究中，Tannenbaum等人已经表明对大剂量hpGRF类似物的GH反应持续存在。
