The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: The former opens to the portal blood and the latter to the cerebrospinal fluid

Rodríguez, Estéban M.; Blázquez, Juan Luis; Guerra, Montserrat

doi:10.1016/j.peptides.2010.01.003

Cited by 259 publications

(231 citation statements)

References 128 publications

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“…These data indicate that brain stem GLP-1Rs can also be targeted by peripherally circulating GLP-1 in line with the aforementioned GLP-1R binding data (28), but whether these acute (0-24 hours) isolated CSF and parenchyma are 100% free of contamination from blood during the procedure, it would be difficult to prove that any measured concentration in CSF and parenchyma could not be an artefact. An alternative but likely hypothesis is that passage into the ARC and the PVN happens via fenestrated capillaries directly from the ME, near the ME-ARC barrier (51). The ARC has been described to have a weak BBB and allow access to certain subpopulations of neurons (57).…”

Section: Discussionmentioning

confidence: 99%

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

Secher¹,

Jelsing²,

Baquero³

et al. 2014

J. Clin. Invest.

722

673

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Section: Discussionmentioning

confidence: 99%

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

Secher¹,

Jelsing²,

Baquero³

et al. 2014

J. Clin. Invest.

722

673

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“…However, the latter express far more abundant NK3R [14], which strongly suggests that ARC NKB neurones projecting to the ME might suppress neurosecretion of GnRH from axon terminals. Because the extracellular milieu of the ME is separated from that of the ARC by the blood-brain barrier [71,72], the only possible sources of NKB reaching GnRH axon terminals are the projections of ARC NKB neurones. Systemic administration of senktide should reach all NK3Rs outside the blood-brain barrier, including those expressed at terminals of GnRH axons in the ME.…”

Section: Mechanisms Of Nkb Suppression Of the Gnrh Pulse Generatormentioning

confidence: 99%

The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

2013

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The KNDy neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn), have been implicated in regulating pulsatile luteinising hormone (LH) secretion. Studies of the interactions between KNDy signalling systems, however, are currently few. Although the stimulatory effect of kisspeptin and the inhibitory effect of Dyn on the gonadotropin-releasing hormone pulse generator are widely accepted, the effects of NKB in rodents are variable and sometimes controversial. Literature describing increased LH secretion in response to NKB receptor agonism predominates and is in line with human physiology, as well as the pathophysiology of pubertal failure associated with disruption of NKB signalling. However, the robust suppression of the LH pulse, induced by the same treatment under hypoestrogenic conditions, may hold clues as to the mechanisms of reproductive inhibition under pathological conditions. This review discusses the recent evidence for this paradox and outlines a revised working model incorporating the mechanisms by which KNDy neuropeptides modulate the reproductive axis.

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“…A number of transcriptional and posttranscriptional mechanisms have evolved to ensure limited expression and tight control of the D2 protein level, which is critical for its homeostatic function (see below). D2 is expressed in the mammalian brain, especially in glial cells; astrocytes and the ependymoglial cells known as tanycytes that line the walls and floor of the third ventricle are particularly important in functional terms as they produce more than 75% of the nuclear T 3 in the rat cerebral cortex (Guadaño-Ferraz et al 1997, Rodríguez et al 2010, Moháacsik et al 2011. Another conspicuous functional distinction between D1/D3 and D2 is the fact that the latter exhibits a remarkable circadian rhythm entrained by the light/dark cycle.…”

Section: The Physiological Role Of Deiodinasesmentioning

confidence: 99%

Iodothyronine deiodinases: a functional and evolutionary perspective

Orozco¹,

Valverde-R²,

Olverá³

et al. 2012

Journal of Endocrinology

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From an evolutionary perspective, deiodinases may be considered pivotal players in the emergence and functional diversification of both thyroidal systems (TS) and their iodinated messengers. To better understand the evolutionary pathway and the concomitant functional diversification of vertebrate deiodinases, in the present review we summarized the highlights of the available information regarding this ubiquitous enzymatic component that represents the final, common physiological link of TS. The information reviewed here suggests that deiodination of tyrosine metabolites is an ancient feature of all chordates studied to date and consequently, that it precedes the integration of the TS that characterize vertebrates. Phylogenetic analysis presented here points to D1 as the oldest vertebrate deiodinase and to D2 as the most recent deiodinase gene, a hypothesis that agrees with the notion that D2 is the most specialized and finely regulated member of the family and plays a key role in vertebrate neurogenesis. Thus, deiodinases seem to be major participants in the evolution and functional expansion of the complex regulatory network of TS found in vertebrates.

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The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: The former opens to the portal blood and the latter to the cerebrospinal fluid

Cited by 259 publications

References 128 publications

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

Iodothyronine deiodinases: a functional and evolutionary perspective

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