Nesfatin-1 and nesfatin-1-like peptide suppress growth hormone synthesis via the AC/PKA/CREB pathway in mammalian somatotrophs

Vélez, Emilio J.; Unniappan, Suraj

doi:10.1038/s41598-020-73840-4

Cited by 21 publications

(26 citation statements)

References 43 publications

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“…An inverse association between GH and irisin levels has been observed in humans, as the administration of recombinant human GH in young patients with Turner syndrome increased the circulating levels of irisin ( 281 ). We have reported that two novel metabolic peptides, nesfatin–1 and nesfatin–1–like peptide, are negative modulators of the synthesis of pituitary GH in mammals ( 166 ). Although their receptors are still unknown, it is expected that these peptides act through GPCR ( 282 ).…”

Section: Other Gh Inhibitorsmentioning

confidence: 99%

“…Although their receptors are still unknown, it is expected that these peptides act through GPCR ( 282 ). It has been shown that both nesfatin–1 and nesfatin–1–like peptide regulate GH in the rat somatotrophs through the AC/PKA/CREB signaling pathway ( 166 ), suggesting that the mechanism of action of nesfatin–1 and nesfatin–1–like peptide involves a GPCR associated with an inhibitory Gα–subunit (Gαi). As discussed in the previous section, numerous pharmacological inhibitors were also used for the study of GH and somatotrophs ( Figure 2 ) .…”

Section: Other Gh Inhibitorsmentioning

confidence: 99%

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A Comparative Update on the Neuroendocrine Regulation of Growth Hormone in Vertebrates

Vélez

Unniappan

2021

Front. Endocrinol.

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Growth hormone (GH), mainly produced from the pituitary somatotrophs is a key endocrine regulator of somatic growth. GH, a pleiotropic hormone, is also involved in regulating vital processes, including nutrition, reproduction, physical activity, neuroprotection, immunity, and osmotic pressure in vertebrates. The dysregulation of the pituitary GH and hepatic insulin-like growth factors (IGFs) affects many cellular processes associated with growth promotion, including protein synthesis, cell proliferation and metabolism, leading to growth disorders. The metabolic and growth effects of GH have interesting applications in different fields, including the livestock industry and aquaculture. The latest discoveries on new regulators of pituitary GH synthesis and secretion deserve our attention. These novel regulators include the stimulators adropin, klotho, and the fibroblast growth factors, as well as the inhibitors, nucleobindin-encoded peptides (nesfatin-1 and nesfatin-1–like peptide) and irisin. This review aims for a comparative analysis of our current understanding of the endocrine regulation of GH from the pituitary of vertebrates. In addition, we will consider useful pharmacological molecules (i.e. stimulators and inhibitors of the GH signaling pathways) that are important in studying GH and somatotroph biology. The main goal of this review is to provide an overview and update on GH regulators in 2020. While an extensive review of each of the GH regulators and an in-depth analysis of specifics are beyond its scope, we have compiled information on the main endogenous and pharmacological regulators to facilitate an easy access. Overall, this review aims to serve as a resource on GH endocrinology for a beginner to intermediate level knowledge seeker on this topic.

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Section: Other Gh Inhibitorsmentioning

confidence: 99%

Section: Other Gh Inhibitorsmentioning

confidence: 99%

A Comparative Update on the Neuroendocrine Regulation of Growth Hormone in Vertebrates

Vélez

Unniappan

2021

Front. Endocrinol.

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“…In a very recent study, both NESF and NLP have been shown to inhibit GH synthesis and its ghrelin-induced release in mammalian somatotrophs ( 120 ). This study was carried out in cultured cell lines (GH3 and RC-4B/C) in which the authors demonstrated that both nucb1 and nucb2 mRNA expression existed, as well as their corresponding NUCB1 and NUCB2 proteins.…”

Section: Nesfatinsmentioning

confidence: 99%

The Complex World of Regulation of Pituitary Growth Hormone Secretion: The Role of Ghrelin, Klotho, and Nesfatins in It

Devesa¹

2021

Front. Endocrinol.

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The classic concept of how pituitary GH is regulated by somatostatin and GHRH has changed in recent years, following the discovery of peripheral hormones involved in the regulation of energy homeostasis and mineral homeostasis. These hormones are ghrelin, nesfatins, and klotho. Ghrelin is an orexigenic hormone, released primarily by the gastric mucosa, although it is widely expressed in many different tissues, including the central nervous system and the pituitary. To be active, ghrelin must bind to an n-octanoyl group (n = 8, generally) on serine 3, forming acyl ghrelin which can then bind and activate a G-protein-coupled receptor leading to phospholipase C activation that induces the formation of inositol 1,4,5-triphosphate and diacylglycerol that produce an increase in cytosolic calcium that allows the release of GH. In addition to its direct action on somatotrophs, ghrelin co-localizes with GHRH in several neurons, facilitating its release by inhibiting somatostatin, and acts synergistically with GHRH stimulating the synthesis and secretion of pituitary GH. Gastric ghrelin production declines with age, as does GH. Klotho is an anti-aging agent, produced mainly in the kidneys, whose soluble circulating form directly induces GH secretion through the activation of ERK1/2 and inhibits the inhibitory effect that IGF-I exerts on GH. Children and adults with untreated GH-deficiency show reduced plasma levels of klotho, but treatment with GH restores them to normal values. Deletions or mutations of the Klotho gene affect GH production. Nesfatins 1 and 2 are satiety hormones, they inhibit food intake. They have been found in GH3 cell cultures where they significantly reduce the expression of gh mRNA and that of pituitary-specific positive transcription factor 1, consequently acting as inhibitors of GH production. This is a consequence of the down-regulation of the cAMP/PKA/CREB signaling pathway. Interestingly, nesfatins eliminate the strong positive effect that ghrelin has on GH synthesis and secretion. Throughout this review, we will attempt to broadly analyze the role of these hormones in the complex world of GH regulation, a world in which these hormones already play a very important role.

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“…We recently reported the first evidence of a GH suppressive effect for nesfatin-1 on rat somatotrophs. 17 Based on this, the pituitary localisation of its mRNA and other evidence on nesfatin-1 effects in fish, we hypothesised that nesfatin-1 is produced in the pituitary somatotrophs and inhibits the GH/IGF axis in goldfish (C. auratus). Here we report the results from our studies testing these hypotheses.…”

mentioning

confidence: 96%

“…16 Another example of a newly identified GH regulator is nesfatin-1. 17 Nesfatin-1 is an 82 amino acid peptide cleaved from the Nterminal of its precursor nucleobindin-2 (NUCB2). This peptide was first discovered in the rat hypothalamus 18 but later identified in other vertebrate groups, including fish.…”

mentioning

confidence: 99%

Nesfatin‐1 is an inhibitor of the growth hormone‐insulin‐like growth factor axis in goldfish (Carassius auratus)

Blanco

Pemberton

et al. 2021

J Neuroendocrinology

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Somatic growth in vertebrates is coordinated by the growth hormone (GH)/insulin-like growth factor (IGF) axis. 1,2 Within this axis, GH is released from the adenohypophysis in response to signals from the hypothalamus. In mammals, GH-releasing hormone (GHRH) and somatostatin are the main hypothalamic peptides regulating GH secretion. 3 However, although GHRH and its receptors are present in earlier evolved vertebrates including teleosts, 4 neuroendocrine control of GH release from teleosts is multifactorial in nature and GHRH has been shown to have little effect on GH secretion in fish 5 ; instead, it is the pituitary adenylate cyclaseactivating polypeptide (PACAP) that has a predominant hypophysiotrophic activity. 6,7 Following its release from the pituitary, the

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Nesfatin-1 and nesfatin-1-like peptide suppress growth hormone synthesis via the AC/PKA/CREB pathway in mammalian somatotrophs

Cited by 21 publications

References 43 publications

A Comparative Update on the Neuroendocrine Regulation of Growth Hormone in Vertebrates

A Comparative Update on the Neuroendocrine Regulation of Growth Hormone in Vertebrates

The Complex World of Regulation of Pituitary Growth Hormone Secretion: The Role of Ghrelin, Klotho, and Nesfatins in It

Nesfatin‐1 is an inhibitor of the growth hormone‐insulin‐like growth factor axis in goldfish (Carassius auratus)

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