7B2, A New Protein Secreted by Human Functionless Pituitary Tumours, in vitro

Venetikou, Maria S.; Ghatei, M. A.; Burrin, J. M.; Latif, Sania; Bloom, Steve

doi:10.1042/cs073043pc

Cited by 4 publications

(5 citation statements)

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“…A correlation between plasma 7B2 and plasma gonadotropins was also reported in menopause and patients suffering from Klinefelter's syndrome, as well as in patients with various human chorionic gonadotropin-secreting tumours of the gastrointestinal tract [134]. In the same vein, 7B2 was shown to be actively secreted by functionless pituitary [133] adenoma, which are often associated with gonadotropin production [139]. High levels of circulating 7B2 have been detected in patients with other specific tumours of neuroendocrine origin.…”

Section: B2 As a Neuroendocrine Markermentioning

confidence: 72%

Neuroendocrine secretory protein 7B2: structure, expression and functions

Mbikay

Seidah

Chrétien

2001

Biochemical Journal

118

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7B2 is an acidic protein residing in the secretory granules of neuroendocrine cells. Its sequence has been elucidated in many phyla and species. It shows high similarity among mammals. A Pro-Pro-Asn-Pro-Cys-Pro polyproline motif is its most conserved feature, being carried by both vertebrate and invertebrate sequences. It is biosynthesized as a precursor protein that is cleaved into an N-terminal fragment and a C-terminal peptide. In neuroendocrine cells, 7B2 functions as a specific chaperone for the proprotein convertase (PC) 2. Through the sequence around its Pro-Pro-Asn-Pro-Cys-Pro motif, it binds to an inactive proPC2 and facilitates its transport from the endoplasmic reticulum to later compartments of the secretory pathway where the zymogen is proteolytically matured and activated. Its C-terminal peptide can inhibit PC2 in vitro and may contribute to keep the enzyme transiently inactive in vivo. The PC2–7B2 model defines a new neuroendocrine paradigm whereby proteolytic activation of prohormones and proneuropeptides in the secretory pathway is spatially and temporally regulated by the dynamics of interactions between converting enzymes and their binding proteins. Interestingly, unlike PC2-null mice, which are viable, 7B2-null mutants die early in life from Cushing's disease due to corticotropin (‘ACTH’) hypersecretion by the neurointermediate lobe, suggesting a possible involvement of 7B2 in secretory granule formation and in secretion regulation. The mechanism of this regulation is yet to be elucidated. 7B2has been shown to be a good marker of several neuroendocrine cell dysfunctions in humans. The possibility that anomalies in its structure and expression could be aetiological causes of some of these dysfunctions warrants investigation.

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Section: B2 As a Neuroendocrine Markermentioning

confidence: 72%

Neuroendocrine secretory protein 7B2: structure, expression and functions

Mbikay

Seidah

Chrétien

2001

Biochemical Journal

118

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“…SgIII is not present in the adrenal medulla but is widely distributed in cells of the anterior pituitary gland [32]. Secretogranin IV protein is abundantly expressed in GH adenomas and focally in null cell adenomas and oncocytomas while secretogranin V shows a similar distribution as secretogranin II [32,35].…”

Section: Discussionmentioning

confidence: 94%

Immunohistochemical Expression of Neuroendocrine Secretory Protein-55 (NESP-55) in Pituitary Adenomas

et al. 2011

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Neuroendocrine secretory protein-55 (NESP-55) is a recently described member of the chromogranin family and appears to be a marker of the constitutive secretory pathway in certain neural, neuroendocrine, and endocrine cell types. It has been shown to be selectively expressed in tumors differentiating towards the adrenal chromaffin and pancreatic islet cell phenotypes. The highest levels of NESP-55 expression, at least in animals, appear to be in the adrenal medulla and the pituitary gland. However, very little is known about the status of NESP-55 expression in pituitary adenomas. We therefore studied the immunohistochemical profile of NESP-55 expression in a series of 30 well-characterized pituitary adenomas (five each of FSH/LH and ACTH, four GH, three TSH, seven prolactin, and six null cells). All tumors were positive for one or more generic marker(s) (chromogranin A, synaptophysin, neuron-specific enolase) of neuroendocrine differentiation. All pituitary adenomas selected for study were stained for NESP-55 with appropriate positive and negative controls. NESP-55 immunoreactivity, seen as brown finely granular cytoplasmic staining of the tumor cells with prominent perinuclear accentuation, was graded as focal (<10% tumor cells staining), moderate (10-50% tumor cells staining), and diffuse (>50% tumor cell staining). Four of seven prolactinomas were positive for NESP-55 (one focal, two moderate, and one diffuse). Two of four GH adenomas were also positive (one focal and one diffuse) while only 1/5 FSH tumors showed a moderately intense immunoreactivity. All other pituitary adenomas were completely negative for NESP-55. Our results indicate that, in human pituitary adenomas, NESP-55 has a more restricted pattern of expression than that of chromogranins A and B. Since immunohistochemical expression of NESP-55 is largely confined to prolactinomas and GH adenomas, it raises the possibility that NESP-55 may somehow be involved in the secretory pathways of these specific cell types.

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“…Although its structure had no homology with the previously known chromogranins, it was similarly identified as a specific biochemical marker of endocrine tissues and secretory granules (4)(5)(6)(7). Unexpectedly, several authors f d e d to detect 7B2 in various types of ACTH-containing tissues suggesting that corticotrophs-contrary to other endocrine cells-might not contain 7B2 (8)(9)(10). In contrast, we have been able to measure immunoreactive human 7B2 in extracts of pituitary, and nonpituitary, tumours responsible for Nelson's syndrome and the ectopic ACTH syndrome.…”

mentioning

confidence: 89%

“…Amounts of POMC and its fragments released in the medium after 60 min of basal ( L l ) or stimulatory( 9 ) incubation. The absolute amounts of POMC and its fragments in the culture media were determined after G75 gel exclusion chromatography.…”

mentioning

confidence: 99%

The Secretory Granule Protein 7B2 is Secreted in Parallel with Proopiomelanocortin and its End‐Products by the Mouse Corticotroph Tumour Cells AtT‐20

Vieau¹,

Tougard²,

Rosenbaum³

et al. 1991

J Neuroendocrinology

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First isolated in porcine pituitary glands the protein 7B2 subsequently proved to be a specific biochemical marker of the secretory granules. Likewise 7B2 was detected in almost all normal and tumoral endocrine tissues. Unexpectedly, several authors failed to demonstrate its presence in rat and human adrenocorticotrophin (ACTH)-secreting cells. In order to definitely establish whether this cell type also produces 7B2 we chose the mouse pituitary corticotroph tumour cell line AtT-20 as a model. Serial dilutions of the mouse culture medium generated displacement curves parallel to that of the standard in a specific 7B2 RIA directed against the human 7B2(23-39) fragment. Under basal secretory conditions immunoreactive 7B2 accumulated in the culture medium in parallel with proopiomelanocortin (POMC) and its fragments N-terminal-joining peptide (NT-JP), joining peptide (JP), beta-lipotropin (beta-LPH), and beta-endorphin (beta-end), although at a much lower (approximately 100-fold) molar concentration. As expected mouse corticotroph cells responded to the stimulatory action of cyclic AMP (3.5 mM) with a preferential increase in the release of POMC end-products, JP and beta-end, which was accompanied by a parallel increase in immunoreactive 7B2 release.

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7B2, A New Protein Secreted by Human Functionless Pituitary Tumours, in vitro

Cited by 4 publications

References 0 publications

Neuroendocrine secretory protein 7B2: structure, expression and functions

Neuroendocrine secretory protein 7B2: structure, expression and functions

Immunohistochemical Expression of Neuroendocrine Secretory Protein-55 (NESP-55) in Pituitary Adenomas

The Secretory Granule Protein 7B2 is Secreted in Parallel with Proopiomelanocortin and its End‐Products by the Mouse Corticotroph Tumour Cells AtT‐20

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