A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats

Abstract

The hypothalamoneurohypophyseal system (HNS) consists of the large peptidergic magnocellular neurons of the supraoptic hypothalamic nucleus (SON) and the paraventricular hypothalamic nucleus (PVN), the axons of which course through the internal zone of the median eminence and terminate at blood capillaries of the posterior lobe of the pituitary gland. The HNS is a specialized brain neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone vasopressin (VP). VP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of VP from magnocellular neuron axon terminals in the posterior pituitary, which is accompanied by a plethora of changes in the morphology, electrophysiological properties, and biosynthetic and secretory activity of the HNS. We wish to understand this functional plasticity in terms of the differential expression of genes. We have therefore used microarrays to comprehensively catalog the genes expressed in the PVN, the SON and the neurointermediate lobe of the pituitary gland of control and dehydrated rats. Comparison of these gene lists has enabled us to identify transcripts that are regulated as a consequence of dehydration as well as RNAs that are enriched in the PVN or the SON. We suggest that these differentially expressed genes represent candidate regulators and effectors of HNS activity and remodeling.T he hypothalamoneurohypophyseal system (HNS) consists of the large peptidergic magnocellular neurons (MCNs) (cell body diameter, 20-40 m) of the supraoptic hypothalamic nuclei (SON) and paraventricular hypothalamic nuclei (PVN), the axons of which course through the internal zone of the median eminence and terminate at blood capillaries of the posterior (neural) lobe of the pituitary gland (1). The SON is a homogenous collection of MCNs, whereas the PVN is divided into a lateral and more medial subdivision of magnocellular and parvocellular neurons respectively. Parvocellular neurons have smaller cells bodies (10-15 m) whose axons project to the external zone of the median eminence (2) and to the brainstem and spinal cord (3). Additional structural and functional components of the HNS include the associated glia (mainly astrocytes with oligodendrocytes and microglia seen rarely), blood vessels, interneurons, and afferent terminals synapsing on MCN somata and dendrites, all of which are intimately associated with MCNs and with each other.The PVN and SON are important integrative structures that regulate coordinated responses to perturbations in cardiovascular homeostasis. Through descending projections from parvocellular neurons to the brainstem, notably the rostral ventrolateral medulla, and intermediolateral cell column of the spinal cord (3), the PVN regulates changes in sympathetic nerve activity involved in blood pressure and blood volume regulation (3). Endocrine responses are mediated through the axonal projections from SON and PVN MCNs to the posterior pituitary. The e...

Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite

“…29). Going beyond, we showed here the functional relevance of dopamine and metabotropic glutamate receptor signaling for sodium appetite, and we identified a specific functional role for D1(5) receptors without effect on a related instinct, thirst for water.…”

Transcription Factor Expression in the Hypothalamo-Neurohypophyseal System of the Dehydrated Rat: Upregulation of Gonadotrophin Inducible Transcription Factor 1 mRNA Is Mediated by cAMP-Dependent Protein Kinase A

“…We hypothesized that alterations in steady-state mRNA levels might be responsible, as least in part, for mediating and regulating SON functional plasticity (Sharman et al, 2004). We have thus used microarrays to compile transcriptome catalogs that, with a high degree of confidence, represent comprehensive descriptions of the RNA populations expressed in the SON (Hindmarch et al, 2006). Furthermore, we identified transcripts that are either upregulated or downregulated as a consequence of chronic dehydration (supplemental Table 2, available at www.…”

“…Interrogation of the Affymetrix 230 2.0 Rat Genome array (Affymetrix, High Wycombe, UK) with targets derived from the SON of control (n ϭ 5) or dehydrated (n ϭ 5) rats has been described (Hindmarch et al, 2006). The Affymetrix Rat 230 2.0 Genome Chips consists of 31,000 oligonucleotide probe sets representing 30,000 transcripts encoded by 28,000 genes.…”

“…Data were analyzed using GeneSpring software version 7.0 (Agilent Technologies, Stockport, UK). After data normalization (Hindmarch et al, 2006), we asked GeneSpring to compile a list of genes called present in all five independent control (C) or dehydrated (D) SON experiments. All marginal, absent, or unknown calls were excluded.…”

Estrogen receptors: Their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis

“…Numerous genes are up regulated in SON during dehydration [21,27,105]. The concurrent decrease in ERβ, a potentially inhibitory transcription factor, identifies genes up-regulated by dehydration as candidates for ERβ inhibition.…”