Kjaer A, Larsen P J, Knigge U, Møller M, Warberg J
Department of Medical Physiology Institute, University of Copenhagen, Denmark.
Endocrinology. 1994 Jan;134(1):482-91. doi: 10.1210/endo.134.1.8275963.
The stimulatory action of centrally administered histamine (HA) on secretion of the anterior pituitary hormones ACTH, beta-endorphin, and PRL is indirect, and previous studies have suggested that hypothalamic neurons containing CRH, arginine vasopressin (AVP), and oxytocin (OT) are involved in this response. We studied the effect of HA on neuronal activation in the hypothalamus by investigating the expression of c-fos, which is a protooncogene activated early when neurons are stimulated. The expression of c-fos was evaluated by detection of c-fos immunoreactivity (c-fos-IR) using immunohistochemistry and by measurement of c-fos mRNA using in situ hybridization techniques. In addition, the identity of the HA-stimulated neurons was investigated by dual antigen immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing increased c-fos expression. HA (270 nmol) infused intracerebroventricularly increased c-fos-IR in the hypothalamus, especially in the periventricular hypothalamic areas and certain hypothalamic nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON). c-fos-immunoreactive nuclei were observed throughout the SON, whereas in the PVN, c-fos-IR was particularly pronounced in the subnuclei known to contain AVP, OT, and CRH neurons. Double labeling experiments confirmed that c-fos was expressed in AVP-, OT-, and CRH-immunoreactive as well as other neurons. In addition, HA intracerebroventricularly induced a moderate expression of c-fos-IR in the arcuate nucleus. In situ hybridization showed increased levels of c-fos mRNA in both the PVN and SON after HA infusion. We conclude that HA-induced secretion of ACTH, beta-endorphin, and PRL may be mediated via activation of hypothalamic AVP, OT, and CRH neurons.
中枢给予组胺（HA）对垂体前叶激素促肾上腺皮质激素（ACTH）、β-内啡肽和催乳素（PRL）分泌的刺激作用是间接的，先前的研究表明，含有促肾上腺皮质激素释放激素（CRH）、精氨酸加压素（AVP）和催产素（OT）的下丘脑神经元参与了这一反应。我们通过研究c-fos的表达来探讨HA对下丘脑神经元激活的影响，c-fos是一种在神经元受到刺激时早期被激活的原癌基因。通过免疫组织化学检测c-fos免疫反应性（c-fos-IR）以及使用原位杂交技术测量c-fos mRNA来评估c-fos的表达。此外，通过双重抗原免疫组织化学观察在显示c-fos表达增加的神经元中AVP-、OT-或CRH-IR，来研究HA刺激的神经元的特性。脑室内注入HA（270 nmol）可增加下丘脑的c-fos-IR，特别是在室周下丘脑区域和某些下丘脑核团，包括室旁核（PVN）和视上核（SON）。在整个SON中都观察到了c-fos免疫反应性核团，而在PVN中，c-fos-IR在已知含有AVP、OT和CRH神经元的亚核中尤为明显。双重标记实验证实c-fos在AVP-、OT-和CRH免疫反应性神经元以及其他神经元中表达。此外，脑室内注入HA可在弓状核中诱导c-fos-IR的适度表达。原位杂交显示注入HA后PVN和SON中的c-fos mRNA水平均升高。我们得出结论，HA诱导的ACTH、β-内啡肽和PRL分泌可能是通过激活下丘脑的AVP、OT和CRH神经元介导的。
