Villar M J, Meister B, Hökfelt T
Department of Neuroscience, Berzelius Laboratory, Karolinska Institutet, Stockholm, Sweden.
J Neurosci. 1994 Oct;14(10):5996-6012. doi: 10.1523/JNEUROSCI.14-10-05996.1994.
Earlier studies have shown the formation of a novel neural lobe after hypophysectomy, an experimental manipulation that causes transection of neurohypophyseal nerve fibers and removal of pituitary hormones. The mechanisms that underly this regenerative process are poorly understood. The localization and number of peptide-immunoreactive (-IR) fibers in the median eminence were studied in normal rats and in rats at different times of survival after hypophysectomy using indirect immunofluorescence histochemistry. The number of vasopressin (VP)-IR fibers increased in the external layer of the median eminence in 5 d hypophysectomized rats. Oxytocin (OXY)-IR fibers decreased in the internal layer and progressively extended into the external layer. At long survival times (9 and 16 months) both VP- and OXY-IR fibers had a bilayered distribution occupying both the external and internal layers. Double-labeling experiments combining VP and tyrosine hydroxylase antisera as well as OXY and growth hormone-releasing factor antisera showed that injured neurosecretory fibers growing into the external layer displaced fibers from parvocellular cells originally located there. As a result, there was essentially an inversion in the distribution of these fibers within the median eminence. Galanin (GAL)- and cholecystokinin (CCK)-IR fibers exhibited a similar pattern of distribution after the lesion. Thus, after 5 d there was an increase in GAL- and CCK-IR fibers in the internal layer. At 14 and 30 d, the number of GAL- and CCK-IR fibers progressively decreased, but after longer survivals (9 and 16 months) there was a dramatic reappearance. Dynorphin (DYN)-LI showed a dramatic increase at all levels of the median eminence at short survival times after hypophysectomy, followed by a subsequent decrease to a final stage of a few, strongly immunoreactive fibers in the external layer at longer survival times. Vasoactive intestinal polypeptide (VIP)- and peptide histidine-isoleucine (PHI)-IR fibers in hypophysectomized animals had already contacted portal vessels 5 d after hypophysectomy, and from then on progressively increased in numbers. Finally, most of the peptide fibers described above formed dense innervation patterns around the large blood vessels along the lateral borders of the median eminence. The present results show that hypophysectomy induces a wide variety of changes in hypothalamic neurosecretory fibers. Not only is the expression of several peptides in these fibers modified following different survival times, but a reorganization of the distribution of immunoreactive fibers within the median eminence is demonstrated. The hypothesis is raised that regeneration of injured neurosecretory fibers may be dependent on changes in the expression of peptides possessing trophic actions.
早期研究表明，垂体切除术后会形成一个新的神经叶，垂体切除术是一种实验性操作，会导致神经垂体神经纤维横断并去除垂体激素。对这一再生过程的潜在机制了解甚少。本研究采用间接免疫荧光组织化学方法，对正常大鼠及垂体切除术后不同存活时间大鼠正中隆起内肽免疫反应（-IR）纤维的定位和数量进行了研究。垂体切除术后5天，正中隆起外层的加压素（VP）-IR纤维数量增加。催产素（OXY）-IR纤维在内层减少，并逐渐延伸至外层。在较长存活时间（9个月和16个月）时，VP-IR纤维和OXY-IR纤维均呈双层分布，占据外层和内层。将VP抗血清与酪氨酸羟化酶抗血清以及OXY抗血清与生长激素释放因子抗血清相结合的双重标记实验表明，生长至外层的受损神经分泌纤维取代了原本位于该处的小细胞的纤维。结果，这些纤维在正中隆起内的分布基本发生了倒置。甘丙肽（GAL）和胆囊收缩素（CCK）-IR纤维在损伤后表现出类似的分布模式。因此，术后5天，内层的GAL-IR纤维和CCK-IR纤维数量增加。在14天和30天时，GAL-IR纤维和CCK-IR纤维数量逐渐减少，但在更长存活时间（9个月和16个月）后又显著重新出现。强啡肽（DYN）-LI在垂体切除术后短存活时间内在正中隆起各水平均显著增加，随后减少，在较长存活时间时在外层形成少数强免疫反应性纤维的最终阶段。垂体切除术后动物的血管活性肠肽（VIP）和肽组氨酸异亮氨酸（PHI）-IR纤维在垂体切除术后5天已与门静脉接触，此后数量逐渐增加。最后，上述大多数肽纤维在正中隆起外侧缘的大血管周围形成密集的神经支配模式。目前的结果表明，垂体切除术会引起下丘脑神经分泌纤维的多种变化。这些纤维中几种肽的表达不仅在不同存活时间后发生改变，而且还证明了正中隆起内免疫反应性纤维分布的重新组织。有人提出假说，受损神经分泌纤维的再生可能依赖于具有营养作用的肽表达的变化。
