Kentroti S, McCann S M
University of Colorado, Health Sciences Center, Denver 80262, USA.
Brain Res Bull. 1996;39(4):201-4. doi: 10.1016/0361-9230(95)02114-0.
The ability of gastrin-releasing peptide to inhibit the release of growth hormone and prolactin by a hypothalamic mechanism has been previously reported. To determine whether or not these effects involved the hypothalamic dopaminergic neurons, ovariectomized female rats were pretreated with the dopamine receptor blocker, pimozide (0.6 mg/kg, SC), or the diluent 35 min prior to administration of gastrin-releasing peptide (2 micrograms in 2 microliters 0.9% NaCl) into the third ventricle. The elevation in plasma growth hormone in response to growth hormone-releasing factor (GRF; 1 microgram/kg, i.v.) was blocked by gastrin-releasing peptide as previously reported following pretreatment with the diluent, but occurred following the injection of pimozide, reversing the inhibitory action of gastrin-releasing peptide. Some control animals that were injected with the pimozide vehicle exhibited elevated plasma prolactin levels compared to levels in uninjected controls. Gastrin-releasing peptide significantly lowered plasma prolactin concentrations in this group of animals. As expected, plasma prolactin levels were elevated following pimozide treatment due to the removal of inhibitory dopaminergic control. Prolactin concentrations were unresponsive to gastrin-releasing peptide treatment in this paradigm and remained elevated throughout the 40-min duration of sampling. We interpret these data to indicate that gastrin-releasing peptide exerts its inhibitory actions on the release of growth hormone and prolactin through a dopaminergic mechanism. Gastrin-releasing peptide may elicit the release of dopamine from tuberoinfundibular neurons, which a) stimulates release of somatostatin, thus inhibiting the release of growth hormone, and b) reaches the pituitary directly via the hypophysial portal vessels to inhibit the release of prolactin from the lactotropes.
胃泌素释放肽通过下丘脑机制抑制生长激素和催乳素释放的能力此前已有报道。为了确定这些作用是否涉及下丘脑多巴胺能神经元，在向第三脑室注射胃泌素释放肽（2微克溶于2微升0.9%氯化钠溶液中）前35分钟，给去卵巢雌性大鼠预先注射多巴胺受体阻滞剂匹莫齐特（0.6毫克/千克，皮下注射）或稀释剂。如先前报道，在用稀释剂预处理后，胃泌素释放肽可阻断生长激素释放因子（GRF；1微克/千克，静脉注射）引起的血浆生长激素升高，但在注射匹莫齐特后这种升高仍会出现，从而逆转了胃泌素释放肽的抑制作用。一些注射了匹莫齐特溶媒的对照动物与未注射的对照动物相比，血浆催乳素水平升高。胃泌素释放肽显著降低了这组动物的血浆催乳素浓度。正如预期的那样，由于去除了抑制性多巴胺能控制，匹莫齐特治疗后血浆催乳素水平升高。在这种模式下，催乳素浓度对胃泌素释放肽治疗无反应，在整个40分钟的采样期间一直保持升高。我们对这些数据的解释是，胃泌素释放肽通过多巴胺能机制对生长激素和催乳素的释放发挥抑制作用。胃泌素释放肽可能会引发结节漏斗神经元释放多巴胺，这会：a）刺激生长抑素释放，从而抑制生长激素释放；b）直接通过垂体门脉血管到达垂体，抑制催乳素细胞释放催乳素。
