Coordinate Expression of Hypothalamic Pro-Dynorphin and Pro-Vasopressin mRNAs with Osmotic Stimulation

Sherman, Thomas G.; Civelli, Olivier; Douglass, James; Herbert, Edward; Watson, Stanley J.

doi:10.1159/000124649

Cited by 135 publications

(47 citation statements)

References 34 publications

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“…Thus, for example, the prodynorphin mRNA, known to be up-regulated in the SON by dehydration (35), is represented by two different probe sets on the array and is identified as being increased in abundance by 1.974-and 1.84-fold. We also note that some probe sets might have failed in some of all of the replicates, thus excluding them from analysis, whereas others might be saturated, which appears to be the fate of the VP probe in the SON.…”

Section: Discussionmentioning

confidence: 99%

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

Hindmarch

Yao

Beighton

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

144

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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...

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Section: Discussionmentioning

confidence: 99%

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

Hindmarch

Yao

Beighton

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

144

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“…A small, but significant increase could also be detected for Hrs-2 mRNA in the SON, while the increase in the PVN was below the levels of statistical significance. It is well known that the mRNA expression of many peptides, such as vasopressin, oxytocin, galanin, dynorphin, cholecystokinin and corticotropin-releasing hormone, as well as the enzyme tyrosine hydroxylase, increase in the PVN and SON after salt-loading [13, 14, 15, 16, 37, 38]. Parallel to the increased synthesis of peptides, there is an increased axonal transport and increased release from the nerve endings in the posterior pituitary accompanied by increased levels in the peripheral circulation [37, 39].…”

Section: Discussionmentioning

confidence: 99%

“…The two nonapeptides are axonally transported to nerve endings in the posterior pituitary, where the hormones are released into the systemic circulation, causing changes in fluid balance and smooth muscle contractility [11]. Upon administration of hyperosmotic stimuli the magnocellular neurons of the PVN and SON undergo several changes, showing an increased mRNA expression for several peptides [12, 13, 14, 15, 16], decreased peptide contents [13, 17, 18]and an increased cell size [19]. During osmotic challenge the hypothalamic magnocellular neurons show an increased secretion rate, which exceeds the rate of transport and mRNA expression, resulting in depletion of the classical hormones vasopressin and oxytocin from nerve endings in the posterior pituitary [13].…”

Section: Introductionmentioning

confidence: 99%

Isoform-Specific Exocytotic Protein mRNA Expression in Hypothalamic Magnocellular Neurons: Regulation after Osmotic Challenge

Jacobsson

Bean²,

Meister

1999

Neuroendocrinology

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Exocytosis is regulated by proteins which interact to promote docking and fusion of secretory granules with the plasma membrane. We have used in situ hybridization to study the mRNA expression for vesicle-associated membrane protein (VAMP) isoforms VAMP-1 and VAMP-2, synaptosomal-associated protein of 25-kDa (SNAP-25) isoforms SNAP-25a and SNAP-25b, mammalian homologue of unc-18 (munc-18) and Hrs-2 in neurosecretory neurons of the magnocellular paraventricular (PVN) and supraoptic (SON) nuclei of normal and osmotically challenged animals. In PVN and SON neurons of normal animals, strong labeling was demonstrated for VAMP-2 and SNAP-25a mRNA, whereas VAMP-1 or SNAP-25b mRNA could not be detected. Salt-loading (2% NaCl as drinking water), an animal model which increases the expression and secretion of hormones from hypothalamic magnocellular neurons, resulted in significantly increased mRNA levels for VAMP-2 (36%, 28%), munc-18 (74%, 68%) and SNAP-25a (59%, 77%) in the PVN and SON, respectively. There was no significant increase in Hrs-2 mRNA levels in the PVN, whereas a significant increase (22%) was observed in the SON. In the posterior pituitary, immunohistochemistry showed a marked decrease in numbers and intensity of vasopressin-immunoreactive (-IR) nerve endings after salt-loading. There were no obvious changes in numbers or intensity of VAMP-2-, munc-18-, Hrs-2- or SNAP-25-IR fibers. Large varicosities containing VAMP-2- and Hrs-2 immunocreactivity were seen in salt-loaded animals. The results show isoform-specific mRNA expression in neurosecretory neurons and an increased mRNA expression of proteins participating in the molecular regulation of exocytosis during an experimental situation characterized by increased secretion.

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“…Pituitaries were homogenized using the LET extraction method to provide material for both mRNA analysis and peptide quantita tion [17]. One fifth of the total volume was separated for further peptide extraction in acetone-0.2 N HCI (3:1).…”

Section: Extraction O F Tissuementioning

confidence: 99%

Development of Pituitary Pro-Opiomelanocortin Gene and Peptide Expression: Characterization and Effect of Repeated Intermittent Maternal Isolation

Vázquez

Akil

1992

Neuroendocrinology

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The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21-day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback.

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Coordinate Expression of Hypothalamic Pro-Dynorphin and Pro-Vasopressin mRNAs with Osmotic Stimulation

Cited by 135 publications

References 34 publications

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

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

Isoform-Specific Exocytotic Protein mRNA Expression in Hypothalamic Magnocellular Neurons: Regulation after Osmotic Challenge

Development of Pituitary Pro-Opiomelanocortin Gene and Peptide Expression: Characterization and Effect of Repeated Intermittent Maternal Isolation

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