60 YEARS OF POMC: POMC: an evolutionary perspective

Navarro, Sandra; Soletto, Lucía; Puchol, Sara; Rotllant, Josep; Soengas, José L.; Cerdá‐Reverter, José Miguel

doi:10.1530/jme-15-0288

Cited by 23 publications

(17 citation statements)

References 33 publications

(36 reference statements)

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“…The ␥-MSH sequence is not present in teleosts and is found as a vestige in non-teleosts, whereas an additional melanocortin peptide, termed ␦-MSH, has been found in cartilaginous fish. This suggests a divergence in MSH sequences in cartilaginous, ray, and lobe-finned fish (266).…”

Section: B the Emergence Of The Precursor Paradigmmentioning

confidence: 98%

“…It is likely that POMC arose over 500 million years ago by an insertion of the melanocortin sequences into a preproendorphin gene. Evidence for this comes from structural identities with other opioid precursors in both the NH 2and COOH-terminal regions of POMC (266). The common opioid gene was thought to arise during chordate evolution.…”

Section: B the Emergence Of The Precursor Paradigmmentioning

confidence: 99%

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POMC: The Physiological Power of Hormone Processing

Harno

Ramamoorthy

Coll

et al. 2018

Physiological Reviews

140

120

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Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon.

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Section: B the Emergence Of The Precursor Paradigmmentioning

confidence: 98%

Section: B the Emergence Of The Precursor Paradigmmentioning

confidence: 99%

POMC: The Physiological Power of Hormone Processing

Harno

Ramamoorthy

Coll

et al. 2018

Physiological Reviews

140

120

View full text Add to dashboard Cite

show abstract

“…Finally, in vitro stimulation of the head kidneys of LR and HR fish with the same concentration of hACTH showed that HR fish had a greater overall outcome and higher relative-to-basal cortisol production compared to LR. It should be noted that the use of the commercially available hACTH should not impede the results of the present study since the structure of ACTH, especially the HFRW and RKRRP (KKRRP in human) core sequences required for receptor binding, are highly conserved, specifically shared from fish to mammals [ 7 , 32 – 34 ]. The substitution of arginine in teleosts to lysine in human in the R(or K)RRP motif has not been shown to interfere with the activation of non-mammalian MC2R by hACTH [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of divergent cortisol responsiveness in European sea bass, Dicentrarchus labrax L.

Σαμαράς¹,

Pavlidis²

2018

PLoS ONE

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Mechanisms regulating differences in cortisol responsiveness between low (LR) and high response (HR) individuals have been poorly studied. In this context, we aimed to study key regulatory processes in cortisol dynamics at the head kidneys of LR and HR European sea bass. To do so, resting plasma cortisol and ACTH concentrations were quantified in these fish. Additionally, the head kidneys of these individuals were superfused through an in vitro superfusion system and stimulated with the same amount of ACTH to assess their cortisol biosynthetic capacity. Moreover, the expression of important genes in cortisol regulation was assessed. Results showed that LR fish had lower resting cortisol concentrations than HR, although no differences existed in the circulating levels of ACTH. Additionally, the biosynthetic capacity of HR was higher than that of LR fish when in vitro stimulated with ACTH. At the molecular level, a statistically significant 3.4-fold higher expression of the ACTH receptor, mc2r, and a 2.3-fold, though not significant, higher expression of 11β-hydroxylase (cyp11b1), an enzyme involved in cortisol biosynthesis, was observed in the HR fish. Finally, a statistically significant 1.3-fold lower expression of 11β-hydroxysteroid dehydrogenase 2 (hsd11b2), an enzyme involved in cortisol inactivation, was observed in HR when compared to LR fish. Therefore, it was for the first time indicated that cortisol dynamics can also be regulated at the post-production level in the head kidney. Collectively, our results highlight the crucial role of the interrenal tissue in the regulation of differences in cortisol response between LR and HR sea bass individuals.

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“…The modulation of opioid signaling by vitamin D3 is one of the major findings of our study. Among the 23 cerebral dysregulated genes that are part of this pathway, three -Pdyn, Penk, Pomc -are noticeable in the cerebrum since they code for endogenous opioids -prodynorphin, dynorphin, leuenkephalin, met-enkephalin, β-endorphinthat are involved in the sensory perception of pain [38]. An intriguing finding is the imbalanced expression of the P trio: Pomc (+5.4) is up-regulated while Pdyn (- (dopamine receptor D2) [41] while Pomc is regulated by Avp [42].…”

Section: A Pomc-related Pain Reliefmentioning

confidence: 99%

Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling

et al. 2019

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The impact of vitamin D on sensory function, including pain processing, has been receiving increasing attention. Indeed, vitamin D deficiency is associated with various chronic pain conditions, and several lines of evidence indicate that vitamin D supplementation may trigger pain relief. However, the underlying mechanisms of action remain poorly understood. We used inflammatory and non-inflammatory rat models of chronic pain to evaluate the benefits of vitamin D3 (cholecalciferol) on pain symptoms. We found that cholecalciferol supplementation improved mechanical nociceptive thresholds in monoarthritic animals and reduced mechanical hyperalgesia and cold allodynia in a model of mononeuropathy. Transcriptomic analysis of cerebrum, dorsal root ganglia and spinal cord tissues indicate that cholecalciferol supplementation induces a massive gene dysregulation which, in the cerebrum, is associated with opioid signaling (23 genes), nociception (14), and allodynia (8), and, in the dorsal root ganglia, with axonal guidance (37 genes), and nociception (17). Among the identified cerebral dysregulated nociception-, allodynia-and opioid-associated genes, 21 can be associated with vitamin D metabolism. However, it appears that their expression is modulated by intermediate regulators such as diverse protein kinases and not, as expected, by the vitamin D receptor. Overall, several genes-Oxt, Pdyn, Penk, Pomc, Pth, Tac1, Tgfb1-encoding for peptides/hormones stand out as top candidates to explain the therapeutic benefit of vitamin D3 supplementation. Further studies are now warranted to detail the precise mechanisms of action but also the most favourable doses and time windows for pain relief.

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60 YEARS OF POMC: POMC: an evolutionary perspective

Cited by 23 publications

References 33 publications

POMC: The Physiological Power of Hormone Processing

POMC: The Physiological Power of Hormone Processing

Regulation of divergent cortisol responsiveness in European sea bass, Dicentrarchus labrax L.

Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling

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