Transcriptomic analysis of the osmotic and reproductive remodelling of the female rat supraoptic nucleus

The supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that co-ordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodelling of the SON, a process known as function-related plasticity. We hypothesise that some of the changes seen in SON remodelling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hydridisation analysis has confirmed the differential expression of 3 of these genes, namely Tumour necrosis factor induced protein 6, Gonadotrophin inducible transcription factor 1 and Ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment respectively), whilst others are consistent with concept of SON morphological plasticity (collagen fibril organisation, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis and homophilic cell adhesion). We suggest that the genes co-ordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON.下丘脑（hypothalamus）的视上核（supraoptic nucleus, SON）是重要的整合性脑结构，可协调机体对水平衡紊乱的应答，并通过向血液循环释放神经肽类激素血管升压素（vasopressin）与催产素（oxytocin），调控母体生理功能。脱水与泌乳均可诱导视上核发生显著的形态重塑，这一过程被称为功能相关可塑性。我们提出假说：视上核重塑过程中的部分变化由差异基因表达介导，因此借助基因微阵列（microarrays）分析了雌性大鼠慢性脱水以及泌乳状态下转录本丰度的全局变化特征。原位杂交（in situ hybridisation）分析已验证其中3个基因的差异表达，分别为肿瘤坏死因子诱导蛋白6（Tumour necrosis factor induced protein 6）、促性腺激素诱导转录因子1（Gonadotrophin inducible transcription factor 1）以及鸟氨酸脱羧酶抗酶抑制因子1（Ornithine decarboxylase antizyme inhibitor 1）。通过对比脱水处理的雌雄大鼠与泌乳大鼠的差异基因表达谱，我们鉴定出了在特定功能基因类别中显著富集的共有调控元件。其中两类元件与生理激活状态下视上核对蛋白质合成与激素分泌的需求升高相关，分别对应翻译起始因子活性（translation initiation factor activity）与内质网-高尔基体中间腔室（endoplasmic reticulum-Golgi intermediate compartment）；其余元件则符合视上核形态可塑性的相关概念，包括胶原纤维组织、细胞外基质组织与生物发生、细胞外结构组织与生物发生以及同型细胞黏附（homophilic cell adhesion）。我们认为，脱水与泌乳诱导下视上核中协同调控的基因可形成调控网络，介导生理激活状态下视上核的可塑性过程。