ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 64 citations in OpenAlex.
- Molecular Abnormalities in BTBR Mice and Their Relevance to Schizophrenia and Autism Spectrum Disorders: An Overview of Transcriptomic and Proteomic Studies.Biomedicines · 2023Article
- Secreted Chaperones in Neurodegeneration.Frontiers in aging neuroscience · 2020Review
- POMC: The Physiological Power of Hormone Processing.Physiological reviews · 2018Review
- Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice.Frontiers in molecular neuroscience · 2015Article
- Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.International journal of molecular sciences · 2013Review
- Pituitary protein 7B2 plasma levels in patients with liver disease: Comparisons with other hormones and neuropeptides.Oncology letters · 2013Article
- Dynamic modulation of prohormone convertase 2 (PC2)-mediated precursor processing by 7B2 protein: preferential effect on glucagon synthesis.The Journal of biological chemistry · 2011Article
- The extended granin family: structure, function, and biomedical implications.Endocrine reviews · 2011Review
- The propeptide precursor proSAAS is involved in fetal neuropeptide processing and body weight regulation.Journal of neurochemistry · 2010Article
- Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs.Frontiers in neuroendocrinology · 2010Review
- Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.Neuroendocrinology · 2009Article
- Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.BMC genetics · 2008Article
- Discovery and progress in our understanding of the regulated secretory pathway in neuroendocrine cells.Histochemistry and cell biology · 2008Review
- Secretory granule neuroendocrine protein 1 (SGNE1) genetic variation and glucose intolerance in severe childhood and adult obesity.BMC medical genetics · 2007Article
- Strain-specific steroidal control of pituitary function.The Journal of endocrinology · 2007Article
- Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation.The Journal of experimental medicine · 2004Article
- Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone.The Journal of clinical investigation · 2004Article
- Regulation of cell growth and expression of 7B2, PC2, and PC1/3 by TGFbeta 1 and sodium butyrate in a human pituitary cell line (HP75).Endocrine · 2003Article
- The chromogranins: their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia.Endocrine pathology · 2003Review
- Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The serine protease prohormone convertase 2 (PC2), principally involved in the processing of polypeptide hormone precursors in neuroendocrine tissues, requires interaction with the neuroendocrine protein 7B2 to generate an enzymatically active form. 7B2 null mice express no PC2 activity and release large quantities of uncleaved ACTH, resulting in a lethal endocrine condition that resembles pituitary Cushing's (Westphal, C. H., Muller, L., Zhou, A., Bonner-Weir, S., Schambelan, M., Steiner, D. F., Lindberg, I. & Leder, P. (1999) Cell 96, 689). Here, we have compared the 7B2 and PC2 null mouse models to determine why the 7B2 null, but not the PC2 null, exhibits a lethal disease state. Both 7B2 and PC2 nulls contained highly elevated pituitary adrenocorticotropic hormone (ACTH); the neurointermediate lobe content of ACTH in 7B2 nulls was 13-fold higher than in WT mice; that of the PC2 null was 65-fold higher. However, circulating ACTH levels were much higher in the 7B2 null than in the PC2 null. Because hypothalamic inhibitory dopaminergic control represents the major influence on intermediate lobe proopiomelanocortin-derived peptide secretion, dopamine levels were measured, and they revealed that 7B2 null pituitaries contained only one-fourth of WT pituitary dopamine. Adrenalectomized 7B2 null animals survived past the usual time of death at 5 weeks; a month after adrenalectomy, they exhibited normal levels of pituitary dopamine, circulating ACTH, and corticosterone. Elevated corticosterone, therefore, seems to play a central role in the lethal phenotype of the 7B2 null, whereas a 7B2-mediated dopaminergic deficiency state may be involved in the actual ACTH hypersecretion phenomenon. Interestingly, adrenalectomized 7B2 nulls also developed unexpectedly severe obesity.
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