Eriksson M, Ceccatelli S, Uvnäs-Moberg K, Iadarola M, Hökfelt T
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Neuroendocrinology. 1996 Apr;63(4):356-67. doi: 10.1159/000126976.
The magnocellular oxytocin neurons within the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus are important relays in the milk ejection reflex in lactating animals, and are activated by suckling. It has been suggested that proto-oncogene transcription factors such as Fos/Jun act as early nuclear transducers of sensory stimuli in neurons. Therefore, we have studied with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal activity in the PVN and SON during suckling in lactating rats. In nonlactating rats, only few cells exhibiting FRAs were observed in these nuclei. Also in lactating rats subjected to continuous suckling Fos-like activity was low. In contrast, lactating rats separated from their pups for 4 h and then exposed to suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin and oxytocin neurons. Using in situ hybridization and immunohistochemistry we have also investigated the expression of the mRNAs for oxytocin, dynorphin, galanin and galanin message-associated peptide and of oxytocin and dynorphin in the PVN of lactating and nonlactating rats. In lactating rats, an increase in oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin and galanin message-associated peptide were downregulated. With the help of immunohistochemistry and double-staining methods, a substantial coexistence between oxytocin- and dynorphin-like immunoreactivities was shown in magnocellular neurons. These results indicate that FRAs are activated in the PVN in the beginning of a suckling period, while this response cannot be seen after continuous stimulation. Furthermore, in the PVN of lactating rats, an upregulation of oxytocin and dynorphin occurs while galanin expression decreases. Finally, the coexistence between oxytocin and dynorphin is more pronounced in lactating rats and nonlactating female rats than has previously been described in male rats.
下丘脑室旁核和视上核(PVN和SON)内的大细胞催产素神经元是泌乳动物排乳反射中的重要中继站,并通过哺乳激活。有人提出,原癌基因转录因子如Fos/Jun作为神经元中感觉刺激的早期核转导器。因此,我们用免疫组织化学方法研究了泌乳大鼠哺乳期间PVN和SON中Fos相关抗原(FRA)作为神经元活动的标志物。在非泌乳大鼠中,在这些核中仅观察到少数显示FRA的细胞。同样,在持续哺乳的泌乳大鼠中,Fos样活性也很低。相反,与幼崽分离4小时然后暴露于哺乳1小时的泌乳大鼠,在加压素和催产素神经元中均表现出强烈的Fos样免疫反应性。我们还使用原位杂交和免疫组织化学研究了泌乳和非泌乳大鼠PVN中催产素、强啡肽、甘丙肽和甘丙肽信息相关肽的mRNA以及催产素和强啡肽的表达。在泌乳大鼠中,观察到催产素和强啡肽及其mRNA增加,而甘丙肽和甘丙肽信息相关肽的mRNA下调。借助免疫组织化学和双重染色方法,在大细胞神经元中显示出催产素样和强啡肽样免疫反应性之间大量共存。这些结果表明,在哺乳期开始时PVN中的FRA被激活,而在持续刺激后看不到这种反应。此外,在泌乳大鼠的PVN中,催产素和强啡肽上调而甘丙肽表达下降。最后,与先前在雄性大鼠中描述的相比,催产素和强啡肽在泌乳大鼠和非泌乳雌性大鼠中的共存更为明显。