垂体前叶神经纤维的功能学研究
摘要
半个世纪前，G.Harris确立了垂体前叶受下丘脑调节的经典理论，
认为垂体前叶受下丘脑正中隆起处释放的促激素调控。垂体前叶内虽
存在有少量的神经纤维，但它们分布于全体前叶血管周围，并不直接
调节腺细胞的分泌。近年来，在大鼠、狗、猴和人的垂体前叶内发现
有相当数量的SP、CGRP等多种免疫反应阳性神经纤维，这些神经纤
维主要集中在腺细胞周围而非血管壁，神经纤维的膨体与腺细胞密切
接触。电镜研究表明在狗和大鼠的垂体前叶内，神经纤维与腺细胞形
成突触联系，强烈提示这些神经纤维可以调节腺细胞的活动。大鼠在
肾上腺或性腺切除等内分泌状态下，垂体前叶神经纤维密度增加，并
存在活跃的芽生现象。所在这些都提示垂体前叶存在直接神经调节，
于是提出了垂体前叶受“神经-体液双重调节”的假说。
我们采用离体灌流结合电场刺激的方法开展垂体前叶神经纤维生
理功能的实验研究。用自制的多头刀架将垂体前叶沿矢状轴切成宽
0.8mm的薄片，置于灌流小室内经KRBGA灌流液平衡30分钟后，
施加电场刺激10分钟，刺激参数为30mA，10Hz，0.5ms。收集每10
分钟的灌流液放免测定ACTH的浓度。每次实验结束前（通常60分
第四军医大学硕士学位论文
钟），用含高r的KRBGA灌流液诱发ACTH的峰值分泌，籍此检测
腺细胞的功能性存活。采用方差分析法进行统计分析，设定灵敏度
P＜0刀5。
实验结果如下：
1．大鼠垂体前叶组织薄片经KRBGA平衡30分钟后，持续灌流50
分钟，ACTH 43efl分泌无明显变化，同样的ACTH的基础分泌不
受1卜M＊TX的影响。
2．用30mA、0．sins、10Hi的电场刺激10分钟可显著抑制ACTH的
基础分泌水平从刺激前平均 163p咖l下降至刺激后 40分钟
89p咖l。电场刺激对 ACTH分泌的抑制作用可被 in M的 TTX完
全阻断。
3．精氨酸加压素门p咖1）可使ACTH的分泌由平均149pg忱1增加
至325pg／ml。电场刺激对精氨酸加压素诱发的ACTH分泌的抑制
作用更加显著。
The clasical theory of hypothalamic control of the anterior pituitary was founded by G. Harris more than half a century ago, which maintains that the anterior pituitary is regulated via hypothalamic hormones secreted at the median eminence but not by direct innervation, albeit it is acknowledged that there is a small amount of autonomic vascular nerve fibres. This concept is recently challenged by the discovery of substantial amount of substance P-and/ or calcitonin gene-related peptide-immunoreactive nerve fibres in the anterior pituitary of rat, dog, monkey, and human. The nerve fibres were found to mainly gather around gland cells, rather than along vascular walls. The varicosities of the nerve fibres could be seen in close proximity to the gland cells. Electron microscopic studies in the dog and rat demonstrated synapses with the gland cells, strongly suggesting that the nerve fibres could regulate the activities of the gland cells. Moreover, changes in endocrine status by adrenalectomy or ovariectomy in the rat profoundly increased the density of the nerve fibres in the anterior pituitary as a result of active axonal sprouting. All these lines of evidence imply a direct neural regulation of the anterior pituitary and a hypothesis of neural-humoral dual regulation of the anterior pituitary has been postulated .However, the physiological significance of the innervation remains an enigma.
We addressed the issue by stimulating the an anterior pituitary slices in vitro. The slices were superfused with Krebs-Ringer bicarbonate-BSA
buffer (KRBGA)in a superfusion chamber for 30min before electrical field stimulation. A square current of 30 mA, lOHz and 0.5ms was then applied for lOmin. The perfusate was collected every lOmin and measured for ACTH by radioimmunoassay. At the end of each experiment (typically 60 min), KRBGA was replaced with high potassium KRBGA to evoke peak ACTH output for assessment of the functional viability of the tissue during the experimental period. Statistic analysis with ANOVA test was done to examine differences between group values, with the limit of significance set atp<0.05. The main results are as fallows:
1. After 30min of equilibration, the KRBGA perfusion was continued for another SOmin. The basal release of ACTH remained constant throughout the experimental period. No significant changes in ACTH basal concentrations were noticed. Similarly, perfusion with KRBGA containing tetrodotxin(TTX, 1 ja M) for the same duration failed to affect the ACTH basal secretion.
2. Electrical field stimulation(EFS)of 30mA, lOHz and 0.5ms for lOmin significantly suppressed basal ACTH concentrations. The suppressive effect of EFS was completely abolished by TTX(1 ju M).
3. The addition of [Args]-vasopressin(10pg/ml) increased ACTH secretion from the basal concentration of 149pg/ml. to 325pg/ml Super-imposition of electrical field stimulation of vasopressin induced -very marked suppression.
认为垂体前叶受下丘脑正中隆起处释放的促激素调控。垂体前叶内虽
存在有少量的神经纤维，但它们分布于全体前叶血管周围，并不直接
调节腺细胞的分泌。近年来，在大鼠、狗、猴和人的垂体前叶内发现
有相当数量的SP、CGRP等多种免疫反应阳性神经纤维，这些神经纤
维主要集中在腺细胞周围而非血管壁，神经纤维的膨体与腺细胞密切
接触。电镜研究表明在狗和大鼠的垂体前叶内，神经纤维与腺细胞形
成突触联系，强烈提示这些神经纤维可以调节腺细胞的活动。大鼠在
肾上腺或性腺切除等内分泌状态下，垂体前叶神经纤维密度增加，并
存在活跃的芽生现象。所在这些都提示垂体前叶存在直接神经调节，
于是提出了垂体前叶受“神经-体液双重调节”的假说。
我们采用离体灌流结合电场刺激的方法开展垂体前叶神经纤维生
理功能的实验研究。用自制的多头刀架将垂体前叶沿矢状轴切成宽
0.8mm的薄片，置于灌流小室内经KRBGA灌流液平衡30分钟后，
施加电场刺激10分钟，刺激参数为30mA，10Hz，0.5ms。收集每10
分钟的灌流液放免测定ACTH的浓度。每次实验结束前（通常60分
第四军医大学硕士学位论文
钟），用含高r的KRBGA灌流液诱发ACTH的峰值分泌，籍此检测
腺细胞的功能性存活。采用方差分析法进行统计分析，设定灵敏度
P＜0刀5。
实验结果如下：
1．大鼠垂体前叶组织薄片经KRBGA平衡30分钟后，持续灌流50
分钟，ACTH 43efl分泌无明显变化，同样的ACTH的基础分泌不
受1卜M＊TX的影响。
2．用30mA、0．sins、10Hi的电场刺激10分钟可显著抑制ACTH的
基础分泌水平从刺激前平均 163p咖l下降至刺激后 40分钟
89p咖l。电场刺激对 ACTH分泌的抑制作用可被 in M的 TTX完
全阻断。
3．精氨酸加压素门p咖1）可使ACTH的分泌由平均149pg忱1增加
至325pg／ml。电场刺激对精氨酸加压素诱发的ACTH分泌的抑制
作用更加显著。
The clasical theory of hypothalamic control of the anterior pituitary was founded by G. Harris more than half a century ago, which maintains that the anterior pituitary is regulated via hypothalamic hormones secreted at the median eminence but not by direct innervation, albeit it is acknowledged that there is a small amount of autonomic vascular nerve fibres. This concept is recently challenged by the discovery of substantial amount of substance P-and/ or calcitonin gene-related peptide-immunoreactive nerve fibres in the anterior pituitary of rat, dog, monkey, and human. The nerve fibres were found to mainly gather around gland cells, rather than along vascular walls. The varicosities of the nerve fibres could be seen in close proximity to the gland cells. Electron microscopic studies in the dog and rat demonstrated synapses with the gland cells, strongly suggesting that the nerve fibres could regulate the activities of the gland cells. Moreover, changes in endocrine status by adrenalectomy or ovariectomy in the rat profoundly increased the density of the nerve fibres in the anterior pituitary as a result of active axonal sprouting. All these lines of evidence imply a direct neural regulation of the anterior pituitary and a hypothesis of neural-humoral dual regulation of the anterior pituitary has been postulated .However, the physiological significance of the innervation remains an enigma.
We addressed the issue by stimulating the an anterior pituitary slices in vitro. The slices were superfused with Krebs-Ringer bicarbonate-BSA
buffer (KRBGA)in a superfusion chamber for 30min before electrical field stimulation. A square current of 30 mA, lOHz and 0.5ms was then applied for lOmin. The perfusate was collected every lOmin and measured for ACTH by radioimmunoassay. At the end of each experiment (typically 60 min), KRBGA was replaced with high potassium KRBGA to evoke peak ACTH output for assessment of the functional viability of the tissue during the experimental period. Statistic analysis with ANOVA test was done to examine differences between group values, with the limit of significance set atp<0.05. The main results are as fallows:
1. After 30min of equilibration, the KRBGA perfusion was continued for another SOmin. The basal release of ACTH remained constant throughout the experimental period. No significant changes in ACTH basal concentrations were noticed. Similarly, perfusion with KRBGA containing tetrodotxin(TTX, 1 ja M) for the same duration failed to affect the ACTH basal secretion.
2. Electrical field stimulation(EFS)of 30mA, lOHz and 0.5ms for lOmin significantly suppressed basal ACTH concentrations. The suppressive effect of EFS was completely abolished by TTX(1 ju M).
3. The addition of [Args]-vasopressin(10pg/ml) increased ACTH secretion from the basal concentration of 149pg/ml. to 325pg/ml Super-imposition of electrical field stimulation of vasopressin induced -very marked suppression.
引文
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90．史轶蘩主编 协和内分泌和代谢学 科学出版社．1997
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