Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies

Vallet, V.; Li, Jacques Y.; Duval, Jacques

doi:10.1016/s0167-0115(96)02110-6

Cited by 18 publications

(15 citation statements)

References 39 publications

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“…Our data from Q-RT-PCR showed that SgII mRNA was overexpressed in tumoral chromaffin tissue compared with normal chromaffin tissue. These results indicate that tumorigenesis of chromaffin cells is accompanied by an increased expression of SgII mRNA, and support the notion that SgII is a useful diagnostic marker for neuroendocrine tumors (Schober et al 1987, Vallet et al 1997. Moreover, in correlation with our microarray study (Thouennon et al 2007), we found that SgII mRNA levels are lower in malignant pheochromocytomas compared with benign pheochromocytomas.…”

Section: Discussionsupporting

confidence: 91%

“…In benign and malignant pheochromocytoma samples examined by western blot, the SgII antibodies revealed the presence of a band with an apparent molecular mass of w97 kDa corresponding to the size of the human SgII protein, as reported previously (Vallet et al 1997; Fig. 2B).…”

Section: Em66 Levels In Pheochromocytoma Extractssupporting

confidence: 87%

“…As observed with the SgII antiserum, we found less immunoreactive bands and lower SgII protein and SgIIderived fragments in malignant tumors compared with benign tumors using antibodies recognizing different regions of the protein. Several studies indicated that SgII processing may vary depending on the tissue or cell type (Dittie & Tooze 1995, Muller & Tougard 1995, Vallet et al 1997, Van Horssen & Martens 1999, Peinado et al 2006. In this study, we showed that two fragments of w46 and w31 kDa were abundant in benign pheochromocytomas.…”

Section: Discussionsupporting

confidence: 53%

“…9212-07, PC1 629-726 ), and PC2 (code no. 7551-05, PC2 529-637 ) were raised in rabbit (Benjannet et al 1993, Vallet et al 1995, 1997, Anouar et al 1996. The mouse monoclonal antibody against actin and the rabbit polyclonal antibody against p-CREB1 were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA).…”

Section: Antibodiesmentioning

confidence: 99%

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Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Guillemot¹,

Thouennon²,

Guérin³

et al. 2012

Journal of Molecular Endocrinology

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We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0 . 95 for the distinction of benign and malignant tumors. Q-PCR experiments indicated that the SgII gene was significantly underexpressed in malignant tumors compared with benign tumors. Western blot analysis using antisera directed against SgII and SgII-derived fragments revealed lower SgII protein and SgII-processing products in malignant tumors. Western blot also showed that low p-cAMP-responsive element-binding (CREB) concentrations seemed to be associated with the malignant status. In addition, the prohormone convertase PC1 and PC2 genes and proteins were overexpressed in benign pheochromocytomas compared with malignant pheochromocytomas. Low concentrations of EM66 found in malignant tumors are associated with reduced expression and production of SgII and SgII-derived peptides that could be ascribed to a decrease in SgII gene transcription, probably linked to p-CREB down-regulation, and to lower PC levels. These findings highlight the mechanisms leading to lower concentrations of EM66 in malignant pheochromocytoma and strengthen the notion that this peptide is a suitable marker of this neuroendocrine tumor.

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Section: Discussionsupporting

confidence: 91%

Section: Em66 Levels In Pheochromocytoma Extractssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 53%

Section: Antibodiesmentioning

confidence: 99%

See 2 more Smart Citations

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Guillemot¹,

Thouennon²,

Guérin³

et al. 2012

Journal of Molecular Endocrinology

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“…The intense EM66-IR observed in all gonadotrophs suggests that this peptide may represent a sensitive circulating marker for the diagnosis of human gonadotrope adenomas. In particular, EM66 may represent a valuable tool to characterize non-functioning pituitary tumors whose secretory granules have been shown to store SgII in the absence of the resident hormones (Rosa et al 1992;Vallet et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Montero-Hadjadje

Pelletier

Yon

et al. 2003

J Histochem Cytochem.

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(YT) S U M M A R Y Characterization of secretogranin II (SgII) mRNA in various vertebrates has revealed selective conservation of the amino acid sequences of two regions of the protein, i.e., the bioactive peptide secretoneurin and a flanking novel peptide that we named EM66. To help elucidate the possible role of EM66, we examined the occurrence as well as the cellular and subcellular distribution of EM66 in rat pituitary and adrenal glands by using a polyclonal antibody raised against the recombinant human EM66 peptide. High-performance liquid chromatography (HPLC) analysis of rat pituitary and adrenal extracts combined with a radioimmunoassay resolved EM66-immunoreactive material exhibiting the same retention time as recombinant EM66. In the rat pituitary, double-labeling immunohistochemical (IHC) studies showed that EM66 immunoreactivity (IR) was present in gonadotrophs, lactotrophs, thyrotrophs, and melanotrophs, whereas corticotrophs were devoid of labeling. EM66-IR was also observed in nerve endings in the neural lobe. Immunocytochemical staining at the electron microscopic level revealed that EM66-IR is sequestered in the secretory granules within gonadotrophs and lactotrophs. In the adrenal medulla, double IHC labeling showed that EM66-IR occurs exclusively in epinephrine-synthesizing cells. At the ultrastructural level, EM66-IR was seen in chromaffin vesicles of adrenomedullary cells. These results demonstrate that post-translational processing of SgII generates a novel peptide that exhibits a cell-specific distribution in the rat pituitary and adrenal glands where it is stored in secretory granules, supporting the notion that EM66 may play a role in the endocrine system.

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Lymphocytic hypophysitis: Report of two biopsy-proven cases and one suspected case with pituitary autoantibodies

Bensing

Höög

et al. 2007

J Endocrinol Invest

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Lymphocytic hypophysitis (LyH) is a rare inflammatory disease, considered to be autoimmune. LyH has mainly been reported in females and in relation to pregnancy or the post-partum period. We describe a 73-yr-old woman and a 63-yr-old male who were evaluated at our clinic because of pituitary hormone deficits. Both patients had pituitary masses suggestive of a pituitary adenoma on magnetic resonance imaging (MRI). Transsphenoidal pituitary surgery was performed and histopathological examinations revealed LyH in both cases. Clinical, laboratory, radiological and the histopathological findings in these two patients are discussed in detail. In addition, we report on a 79-yr-old man with partial hypopituitarism and empty sella. Screening of a human pituitary cDNA library with his serum revealed autoantibodies against secretogranin II. This is a protein commonly present in human gonadotrophs, thyreotrophs and corticotrophs. Since the patient selectively showed the corresponding pituitary insufficiencies, we speculate on an autoimmune background. Further studies may ascertain the importance of secretogranin II autoantibodies as markers for LyH.

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Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies

Cited by 18 publications

References 39 publications

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Lymphocytic hypophysitis: Report of two biopsy-proven cases and one suspected case with pituitary autoantibodies

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