Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

Raffin-Sanson, Marie Laure; Keyzer, Yves de; Bertagna, Xavier

doi:10.1530/eje.0.1490079

Cited by 222 publications

(132 citation statements)

References 91 publications

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“…The proopiomelanocortin gene (POMC) is expressed in a relatively small group of neurons that originate in the developing ventral hypothalamus of all jawed vertebrates (10,11). Pomcexpressing neurons mature in the arcuate nucleus of the hypothalamus, integrate into neuronal circuits that become fully functional after weaning, and continue to actively express Pomc throughout the life span (12).…”

Section: Convergent Evolution Of Two Mammalian Neuronal Enhancers By mentioning

confidence: 99%

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Franchini

López-Leal

Nasif

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

121

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The proopiomelanocortin gene ( POMC ) is expressed in a group of neurons present in the arcuate nucleus of the hypothalamus. Neuron-specific POMC expression in mammals is conveyed by two distal enhancers, named nPE1 and nPE2. Previous transgenic mouse studies showed that nPE1 and nPE2 independently drive reporter gene expression to POMC neurons. Here, we investigated the evolutionary mechanisms that shaped not one but two neuron-specific POMC enhancers and tested whether nPE1 and nPE2 drive identical or complementary spatiotemporal expression patterns. Sequence comparison among representative genomes of most vertebrate classes and mammalian orders showed that nPE1 is a placental novelty. Using in silico paleogenomics we found that nPE1 originated from the exaptation of a mammalian-apparent LTR retrotransposon sometime between the metatherian/eutherian split (147 Mya) and the placental mammal radiation (≈90 Mya). Thus, the evolutionary origin of nPE1 differs, in kind and time, from that previously demonstrated for nPE2, which was exapted from a CORE-short interspersed nucleotide element (SINE) retroposon before the origin of prototherians, 166 Mya. Transgenic mice expressing the fluorescent markers tomato and EGFP driven by nPE1 or nPE2, respectively, demonstrated coexpression of both reporter genes along the entire arcuate nucleus. The onset of reporter gene expression guided by nPE1 and nPE2 was also identical and coincidental with the onset of Pomc expression in the presumptive mouse diencephalon. Thus, the independent exaptation of two unrelated retroposons into functional analogs regulating neuronal POMC expression constitutes an authentic example of convergent molecular evolution of cell-specific enhancers.

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Section: Convergent Evolution Of Two Mammalian Neuronal Enhancers By mentioning

confidence: 99%

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Franchini

López-Leal

Nasif

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

121

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“…This precursor contains melanotropins (MSH), corticotropins (ACTH), corticotropin-like intermediate peptide (CLIP), lipotropins (LPH),ˇ-endorphin and met-enkephalin, all of which have different functions. 62 It is therefore important in a peptidomic study to identify all peptides originating from a precursor since each of these peptides might have a different physiological relevance. In insects similar observations are made, On precursor can contain different unrelated peptides.…”

Section: Discussionmentioning

confidence: 99%

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

et al. 2005

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Peptides are the largest class of signalling molecules found in animals. Nevertheless, in most proteomic studies peptides are overlooked since they literally fall through the mazes of the net. In analogy with proteomics technology, where all proteins expressed in a cell or tissue are analyzed, the peptidomic approach aims at the simultaneous visualization and identification of the whole peptidome of a cell or tissue, i.e. all expressed peptides with their post-translational modifications. In this paper we describe the analysis of the larval fruit fly central nervous system using two-dimensional capillary liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF-MS/MS. Using the central nervous systems of only 50 larval Drosophila as starting material, we identified 38 peptides in a single analysis, 20 of which were not detected in a previous study that reported on the one-dimensional capillary LC/MS/MS analysis of the same tissue. Among the 38 sequenced peptides, some originate from precursors, such as the tachykinin and the IFamide precursor that were entirely missed in the first study. This clearly demonstrates that the two-dimensional capillary LC approach enhances the coverage of the peptidomic analysis.

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“…The corticotrophinomas of Nelson's syndrome and Cushing's disease originate from the same corticotroph cells: POMC mRNA is identical to that expressed in normal corticotroph cells and is processed in the usual way (63). There are histological and molecular similarities between these two tumour types (61,64).…”

Section: What Is the Aetiology Of Nelson's Syndrome?mentioning

confidence: 99%

Nelson's syndrome

Barber

Adams²,

Ansorge³

et al. 2010

European Journal of Endocrinology

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Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (O500 ng/l) in addition to progressive elevations of ACTH (a rise of O30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

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Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

Cited by 222 publications

References 91 publications

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two‐dimensional capillary liquid chromatography quadrupole time‐of‐flight mass spectrometry

Nelson's syndrome

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