Effects of neuromedin-k on the rat hypothalamo pituitary-adrenal axis

Malendowicz, L K; Nussdorfer, Gastone G.; Markowska, Anna; Macchi, C; Nowak, Krzysztof W.; Butowska, W

doi:10.1016/0143-4179(95)90005-5

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…Senktide also induced a robust increase in circulating CORT levels, indicative of potent HPA axis activation. This is in agreement with a previous report of raised plasma ACTH and CORT levels following sc administration of NKB (72). Furthermore, because SB222200 blocked the suppressive effect of LPS on the LH pulse, NKB is likely released in response to LPS and might contribute to the activation of pituitary corticotropes that underlies adrenal glucocorticoid secretion.…”

supporting

confidence: 90%

Neurokinin B Signaling in the Female Rat: a Novel Link Between Stress and Reproduction

Grachev

Li²,

Hu³

et al. 2014

Endocrinology

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Acute systemic stress disrupts reproductive function by inhibiting pulsatile gonadotropin secretion. The underlying mechanism involves stress-induced suppression of the GnRH pulse generator, the functional unit of which is considered to be the hypothalamic arcuate nucleus kisspeptin/neurokinin B/dynorphin A neurons. Agonists of the neurokinin B (NKB) receptor (NK3R) have been shown to suppress the GnRH pulse generator, in a dynorphin A (Dyn)-dependent fashion, under hypoestrogenic conditions, and Dyn has been well documented to mediate several stress-related central regulatory functions. We hypothesized that the NKB/Dyn signaling cascade is required for stress-induced suppression of the GnRH pulse generator. To investigate this ovariectomized rats, iv administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular pretreatment with NK3R or κ-opioid receptor (Dyn receptor) antagonists, were subjected to frequent blood sampling for hormone analysis. Antagonism of NK3R, but not κ-opioid receptor, blocked the suppressive effect of LPS challenge on LH pulse frequency. Neither antagonist affected LPS-induced corticosterone secretion. Hypothalamic arcuate nucleus NKB neurons project to the paraventricular nucleus, the major hypothalamic source of the stress-related neuropeptides CRH and arginine vasopressin (AVP), which have been implicated in the stress-induced suppression of the hypothalamic-pituitary-gonadal axis. A separate group of ovariectomized rats was, therefore, used to address the potential involvement of central CRH and/or AVP signaling in the suppression of LH pulsatility induced by intracerebroventricular administration of a selective NK3R agonist, senktide. Neither AVP nor CRH receptor antagonists affected the senktide-induced suppression of the LH pulse; however, antagonism of type 2 CRH receptors attenuated the accompanying elevation of corticosterone levels. These data indicate that the suppression of the GnRH pulse generator by acute systemic stress requires hypothalamic NKB/NK3R signaling and that any involvement of CRH therewith is functionally upstream of NKB.

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confidence: 90%

Neurokinin B Signaling in the Female Rat: a Novel Link Between Stress and Reproduction

Grachev

Li²,

Hu³

et al. 2014

Endocrinology

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“…For this reason, we investigated the possible involvement of CRF and related stress-associated neuropeptide, arginine vasopressin (AVP), in mediating the suppressive effects of central administration of senktide on the HPG axis. Despite evidence that central administration of NK3R agonists induces expression of c-Fos (marker of neuronal activation) in CRF and AVP neurones [80,81] and increases adrenocorticotrophic hormone and corticosterone release [82], neither CRF nor AVP receptor antagonists prevented the senktide-induced suppression of the GnRH pulse generator [83]. ARC NKB neurones are therefore unlikely to recruit these elements of the HPA axis to suppress the GnRH pulse generator.…”

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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“…NMU has been shown to affect hormonal systems, including a profound effect on the in vivo release of stress-related modulators from the anterior pituitary and adrenal glands (12). Corticotrophs within the anterior lobe of rat and human pituitary gland contain high levels of NMU-like immunoreactivity (13), suggesting a hormonal role for NMU.…”

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confidence: 99%

Identification and Characterization of Two Neuromedin U Receptors Differentially Expressed in Peripheral Tissues and the Central Nervous System

Raddatz¹,

Wilson²,

Artymyshyn³

et al. 2000

Journal of Biological Chemistry

193

175

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Two structurally related, G-protein-coupled receptors were identified as receptors for the neuropeptide, neuromedin U. This peptide is found in highest levels in the gut and genitourinary system where it potently contracts smooth muscle but is also expressed in the spinal cord and discrete regions of the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar potency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative reverse transcription-polymerase chain reaction in a variety of human tissues shows distinct expression patterns for the two receptors. NMU1 is expressed predominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtypes will greatly aid in the determination of the physiological roles of this peptide.

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Effects of neuromedin-k on the rat hypothalamo pituitary-adrenal axis

Cited by 10 publications

References 16 publications

Neurokinin B Signaling in the Female Rat: a Novel Link Between Stress and Reproduction

Neurokinin B Signaling in the Female Rat: a Novel Link Between Stress and Reproduction

The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

Identification and Characterization of Two Neuromedin U Receptors Differentially Expressed in Peripheral Tissues and the Central Nervous System

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