Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours
| العنوان: | Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours |
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| المؤلفون: | Patrick J. Kenny, Márta Korbonits, Jordan E. Read, Stijn J. M. Niessen, Victoria J Crossley, Samantha M. Mirczuk, Christopher J Scudder, Jacob T. Regan, Robert C. Fowkes, Imelda M. McGonnell, Craig A. McArdle, Holger A. Volk, Caroline P.D. Wheeler-Jones, David B. Church, Bigboy H. Simbi, Joe Fenn, Karen M. Richardson |
| المساهمون: | McArdle, Craig A [0000-0003-4836-5351], Fenn, Joseph [0000-0001-7851-670X], Volk, Holger A [0000-0002-7312-638X], Wheeler-Jones, Caroline P [0000-0002-6542-7713], Fowkes, Robert C [0000-0002-2222-2056], Apollo - University of Cambridge Repository |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 3 International Journal of Molecular Sciences, Vol 22, Iss 1076, p 1076 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Growth hormone receptor, pituitary, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Natriuretic peptide, Cyclic AMP, feline, Receptor, lcsh:QH301-705.5, Cyclic GMP, Thyrotropin-Releasing Hormone, Spectroscopy, Forskolin, General Medicine, NPR1, NPR2, Computer Science Applications, medicine.anatomical_structure, Phenotype, Pituitary Gland, CNP, Female, medicine.medical_specialty, Somatotropic cell, medicine.drug_class, 030209 endocrinology & metabolism, Biology, Catalysis, Article, Cell Line, Inorganic Chemistry, 03 medical and health sciences, Anterior pituitary, Internal medicine, medicine, Animals, Pituitary Neoplasms, Physical and Theoretical Chemistry, Rats, Wistar, Molecular Biology, multiplex RT-qPCR, Organic Chemistry, somatotrope, Colforsin, Estrogens, Natriuretic Peptide, C-Type, Rats, 030104 developmental biology, Endocrinology, chemistry, lcsh:Biology (General), lcsh:QD1-999, Acromegaly, Mutation, Cats, Receptors, Atrial Natriuretic Factor |
| الوصف: | Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µ M forskolin, yet only Npr1 expression was sensitive to forskolin stimulation the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes. |
| وصف الملف: | application/pdf; application/zip; text/xml |
| DOI: | 10.17863/cam.63742 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::593fe57698d38b23f163bc92b3a67c7b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....593fe57698d38b23f163bc92b3a67c7b |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.17863/cam.63742 |
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