McCann S M, Vijayan E
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Ann N Y Acad Sci. 1992;668:287-97. doi: 10.1111/j.1749-6632.1992.tb27357.x.
Neurotensin is localized in discrete populations of neuronal cell bodies with terminals in the hypothalamus and median eminence. High-affinity binding sites for neurotensin have been demonstrated not only in the hypothalamus but also in the pituitary gland. These studies suggest a role for neurotensin in control of hypothalamic-pituitary function. We initially demonstrated that neurotensin could block the release of prolactin in conscious, ovariectomized and male rats after its injection into the third ventricle, whereas intravenous injection of the peptide significantly elevated plasma prolactin and increased prolactin release by pituitaries incubated in vitro. These results suggested that neurotensin had opposite actions on prolactin release, an inhibitory effect at a hypothalamic site and an excitatory one at the pituitary. Further studies employing dopamine receptor blockers and inhibitors of catecholamine synthesis indicated that the action of the peptide to block prolactin release was probably mediated by release of dopamine, which then inhibited prolactin release by the pituitary gland directly. We have evaluated the physiological significance of the peptide in control of prolactin release by intraventricular injection of highly specific antiserum against neurotensin. The antiserum evoked dose-related elevations in plasma prolactin in intact males that were significant but smaller in magnitude than those seen in females, actions opposite to those of the peptide itself, which indicates that the inhibitory action of the peptide within the brain is physiologically significant. Intravenous injection of this antiserum produced a significant suppression of plasma prolactin in females but not males, which indicates that the previously demonstrated stimulatory effect of the peptide on prolactin release by the gland is also physiologically significant because immunoneutralization of the peptide resulted in a decline in plasma prolactin. Our earlier experiments revealed that neurotensin had a dose-related ability to inhibit LH release in ovariectomized and ovariectomized, estrogen progesterone-treated rats. Since it had no effect on the release of LH in vitro, we assigned a hypothalamic site for this action. It appears that this inhibitory effect of the peptide to suppress LH release is also physiologically significant since the intraventricular injection of the antiserum against the peptide produced a dose-related stimulation of LH release in ovariectomized and ovariectomized, estrogen progesterone-blocked rats. The mechanism by which endogenous neurotensin inhibits the release of LHRH has yet to be evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)
神经降压素定位于神经元细胞体的离散群体中，其终末位于下丘脑和正中隆起。不仅在下丘脑中，而且在垂体中都已证实存在神经降压素的高亲和力结合位点。这些研究提示神经降压素在控制下丘脑 - 垂体功能中起作用。我们最初证明，将神经降压素注入第三脑室后，可阻断清醒、去卵巢和雄性大鼠催乳素的释放，而静脉注射该肽则可显著提高血浆催乳素水平，并增加体外培养垂体的催乳素释放。这些结果提示神经降压素对催乳素释放有相反的作用，在下丘脑部位起抑制作用，在垂体部位起兴奋作用。进一步使用多巴胺受体阻滞剂和儿茶酚胺合成抑制剂的研究表明，该肽阻断催乳素释放的作用可能是由多巴胺释放介导的，多巴胺随后直接抑制垂体释放催乳素。我们通过脑室内注射针对神经降压素的高度特异性抗血清，评估了该肽在控制催乳素释放中的生理意义。抗血清在完整雄性大鼠中引起血浆催乳素与剂量相关的升高，虽有显著性但幅度小于雌性大鼠，其作用与该肽本身相反，这表明该肽在脑内的抑制作用具有生理意义。静脉注射这种抗血清可显著抑制雌性大鼠而非雄性大鼠的血浆催乳素，这表明该肽先前显示的对腺体催乳素释放的刺激作用也具有生理意义，因为该肽的免疫中和导致血浆催乳素下降。我们早期的实验表明，神经降压素在去卵巢以及去卵巢并用雌激素和孕激素处理的大鼠中具有与剂量相关的抑制促黄体生成素释放的能力。由于它在体外对促黄体生成素的释放没有影响，我们认为该作用位点在下丘脑。似乎该肽抑制促黄体生成素释放的这种抑制作用也具有生理意义，因为脑室内注射针对该肽的抗血清在去卵巢以及去卵巢并用雌激素和孕激素阻断的大鼠中引起促黄体生成素释放与剂量相关的刺激。内源性神经降压素抑制促性腺激素释放激素释放的机制尚待评估。（摘要截选至400字）
