Kentroti S, Dees W L, McCann S M
University of Texas Health Science Center, Department of Physiology, Dallas 75235.
Proc Natl Acad Sci U S A. 1988 Feb;85(3):953-7. doi: 10.1073/pnas.85.3.953.
Gastrin-releasing peptide (GRP) is localized to hypothalamic neurons and is a potent inhibitor of basal and growth hormone (GH)-releasing factor-induced GH secretion in the rat. It also acts similarly to inhibit opiate- and stress-induced prolactin (PRL) release. To determine the physiological significance of the peptide in the control of the release of these two hormones, a highly specific antiserum against GRP was injected into the third brain ventricle to immunoneutralize hypothalamic GRP. The injection of the antiserum initially did not alter levels of the hormones; however, both PRL and GH levels in the plasma began to increase within 3 and 3.5 hr, respectively. They were still significantly elevated 24 hr after the injection. There was no change in the plasma levels of either hormone in animals injected intraventricularly with a similar volume of normal rabbit serum (NRS). Mean plasma GH levels 24 hr after antiserum injection were more than twice those of the NRS-injected controls, whereas the PRL concentrations were 14-fold higher in the antiserum injected as compared to the control NRS-injected animals. A second similar injection of antiserum 24 hr after the first administration resulted in a slight and transient further increase in both GH and PRL levels so that they were both significantly (P less than 0.001) higher than those of the animals given a second injection of NRS. The anti-GRP antiserum was highly specific for GRP by radioimmunoassay procedures and this antiserum produced positive immunostaining of GRP neuronal perikarya and terminals within discrete hypothalamic nuclei. Beaded fibers and terminals were observed in the suprachiasmatic nucleus (SCN) and the area lateral and dorsal to the SCN in the region of the periventricular nucleus (PeVN). GRP-positive perikarya were observed in the parvocellular neurons of the paraventricular nucleus. In addition, GRP-positive cell bodies were observed in the PeVN in close proximity to the third ventricle. Furthermore, the median eminence displayed no immunostaining for GRP, and all traces of positive staining were abolished by preabsorption of the antiserum with GRP-27 (30 micrograms/ml), confirming the specificity of the antiserum. The combined results with immunoneutralization of GRP and the immunostaining of GRP neuronal elements in the hypothalamus support the physiological role of this peptide in the inhibitory control of both GH and PRL release.
胃泌素释放肽（GRP）定位于下丘脑神经元，是大鼠基础及生长激素释放因子诱导的生长激素（GH）分泌的强效抑制剂。它在抑制阿片类物质和应激诱导的催乳素（PRL）释放方面也有类似作用。为确定该肽在这两种激素释放调控中的生理意义，将一种针对GRP的高度特异性抗血清注入第三脑室，以免疫中和下丘脑的GRP。注射抗血清最初并未改变激素水平；然而，血浆中的PRL和GH水平分别在3小时和3.5小时内开始升高。注射后24小时，它们仍显著升高。向脑室内注射相同体积正常兔血清（NRS）的动物，两种激素的血浆水平均无变化。注射抗血清24小时后的平均血浆GH水平是注射NRS的对照组的两倍多，而与注射对照NRS的动物相比，注射抗血清的动物PRL浓度高14倍。在首次给药24小时后再次进行类似的抗血清注射，导致GH和PRL水平均有轻微且短暂的进一步升高，使其均显著高于（P小于0.001）接受第二次NRS注射的动物。通过放射免疫分析程序，抗GRP抗血清对GRP具有高度特异性，且该抗血清在离散的下丘脑核内对GRP神经元胞体和终末产生阳性免疫染色。在视交叉上核（SCN）以及室周核（PeVN）区域中SCN外侧和背侧区域观察到串珠状纤维和终末。在室旁核的小细胞神经元中观察到GRP阳性胞体。此外，在靠近第三脑室的PeVN中观察到GRP阳性细胞体。此外，正中隆起未显示GRP免疫染色，并且通过用GRP - 27（30微克/毫升）预吸收抗血清消除了所有阳性染色痕迹，证实了抗血清的特异性。GRP免疫中和及下丘脑GRP神经元成分免疫染色的综合结果支持了该肽在抑制GH和PRL释放方面的生理作用。
