Ghrelin-Induced Enhancement of Vasopressin and Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures

Gálfi, Márta; Radács, Marianna; Molnár, Zs.; Budai, I.; Tóth, Gábor; Pósa, Anikó; Kupai, Krisztina; Szalai, Zita; Szabó, Renáta; Molnár, H Andor; Gardi, János; László, Ferenc; Varga, Csaba

doi:10.1007/s12031-016-0850-4

Cited by 11 publications

(13 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OT is present in pre-autonomic neurons (Sawchenko and Swanson, 1982), which indicates this peptide is involved in the control of these responses. The present results, together with the observations of effects caused by intra-PVN administration of ghrelin on food intake (Wren et al, 2001; Melis et al, 2002; Olszewski et al, 2003; Shrestha et al, 2004); and effects of ghrelin on neuroendocrine (Wren et al, 2002; Gálfi et al, 2016) and autonomic control (Matsumura et al, 2002; Yasuda et al, 2003; Theander-Carrillo et al, 2006; Tanida et al, 2007) indicate the PVN as a major site of action for ghrelin, therefore contributing to the response to caloric imbalance.…”

Section: Discussionsupporting

confidence: 70%

“…Intra-cerebro ventricular ghrelin increases FOS expression on OT neurons in the PVN (Olszewski et al, 2007), and ghrelin induces OT release in hypothalamic cell culture (Gálfi et al, 2016). The release of OT in response to ghrelin, however, has not been demonstrated in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…These neuroendocrine effects suggest effects on corticotropin releasing hormone (CRH) and thyrotropin releasing hormone (TRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus. In vitro , ghrelin induces AVP and CRH release in hypothalamic explants (Wren et al, 2002; Mozid et al, 2003), and oxytocin (OT) and AVP release in neurohypophyseal cell culture (Gálfi et al, 2016). Food deprivation, which increases ghrelin, reduces TRH (Mori et al, 1988; Blake et al, 1991), and TRH-mRNA levels in the brain decrease after peripheral ghrelin injection, suggesting that TRH neurons are affected by ghrelin (Pekary and Sattin, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons

Dos‐Santos

Grover

Reis

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The paraventricular nucleus (PVN) is involved in the control of sympathetic tone and the secretion of hormones, both functions known to be influenced by ghrelin, suggesting direct effect of ghrelin in this nucleus. However, the effects of ghrelin on the excitability of different PVN neuronal populations have not been demonstrated. This study assessed the effects of ghrelin on the activity of PVN neurons, correlating the responses to subpopulations of PVN neurons. We used a 64 multielectrode array to examine the effects of ghrelin administration on extracellular spike frequency in PVN neurons recorded in brain slices obtained from male Sprague-Dawley rats. Bath administration of 10 nM ghrelin increased (29/97, 30%) or decreased (37/97, 38%) spike frequency in PVN neurons. The GABAA and glutamate receptors antagonists abolish the decrease in spike frequency, without changes in the proportion of increases in spike frequency (23/53, 43%) induced by ghrelin. The results indicate a direct effect of ghrelin increasing PVN neurons activity and a synaptic dependent effect decreasing PVN neurons activity. The patch clamp recordings showed similar proportions of PVN neurons influenced by 10 nM ghrelin (33/95, 35% depolarized; 29/95, 30% hyperpolarized). Using electrophysiological fingerprints to identify specific subpopulations of PVN neurons we observed that the majority of pre-autonomic neurons (11/18 -61%) were depolarized by ghrelin, while both neuroendocrine (29% depolarizations, 40% hyperpolarizations), and magnocellular neurons (29% depolarizations, 21% hyperpolarizations) showed mixed responses. Finally, to correlate the electrophysiological response and the neurochemical phenotype of PVN neurons, cell cytoplasm was collected after recordings and RT-PCR performed to assess the presence of mRNA for vasopressin, oxytocin, thyrotropin (TRH) and corticotropin (CRH) releasing hormones. The single-cell RT-PCR showed that most TRH-expressing (4/5) and CRH-expressing (3/4) neurons are hyperpolarized in response to ghrelin. In conclusion, ghrelin either directly increases or indirectly decreases the activity of PVN neurons, this suggests that ghrelin acts on inhibitory PVN neurons that, in turn, decrease the activity of TRH-expressing and CRH-expressing neurons in the PVN.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons

Dos‐Santos

Grover

Reis

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Intravenous administration of ghrelin increases AVP in humans . In rats, the ICV administration of ghrelin increases plasma AVP levels, and ghrelin increases AVP release from hypothalamic explants . We previously demonstrated mixed effects of ghrelin on AVP mgPVN neurons .…”

Section: The Pvn As a Mediator Of The Neuroendocrine Actions Of Ghrelinmentioning

confidence: 94%

“…Peripheral administration of ghrelin increases plasma levels of OT and ICV ghrelin administration increases c‐FOS in OT PVN neurons in rats. In hypothalamic cell cultures, ghrelin increases OT release; however, these effects can be blocked by GHSR antagonist . Gastric electrical stimulation, a treatment for obesity that activates satiety‐related neurons in the hypothalamus, increases the expression of OT in the mgPVN and supraoptic nucleus (SON), while at the same time decreasing the expression of ghrelin in the same nuclei .…”

Section: The Pvn As a Mediator Of The Neuroendocrine Actions Of Ghrelinmentioning

confidence: 99%

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Dos‐Santos

Reis

Perelló³

et al. 2019

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Ghrelin is a peptide mainly produced and secreted by the stomach. Since its discovery, the impact of ghrelin on the regulation of food intake has been the most studied function of this hormone; however, ghrelin affects a wide range of physiological systems, many of which are controlled by the hypothalamic paraventricular nucleus (PVN). Several pathways may mediate the effects of ghrelin on PVN neurons, such as direct or indirect effects mediated by circumventricular organs and/or the arcuate nucleus. The ghrelin receptor is expressed in PVN neurons, and the peripheral or intracerebroventricular administration of ghrelin affects PVN neuronal activity. Intra-PVN application of ghrelin increases food intake and decreases fat oxidation, which chronically contribute to the increased adiposity. Additionally, ghrelin modulates the neuroendocrine axes controlled by the PVN, increasing the release of vasopressin and oxytocin by magnocellular neurons and corticotropin-releasing hormone by neuroendocrine parvocellular neurons, while possibly inhibiting the release of thyrotropin-releasing hormone. Thus, the PVN is an important target for the actions of ghrelin. Our review discusses the mechanisms of ghrelin actions in the PVN, and its potential implications for energy balance, neuroendocrine, and integrative physiological control.

show abstract

Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers

et al. 2021

View full text Add to dashboard Cite

Purpose The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated. Methods In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg). Results Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [− 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: − 0.13 [− 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (− 0.18 [− 0.22, − 0.09] mU/L, p < 0.001). Conclusion We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones. Registration The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.

show abstract

Ghrelin-Induced Enhancement of Vasopressin and Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures

Cited by 11 publications

References 54 publications

Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons

Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers

Contact Info

Product

Resources

About