Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours

Autor: 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
Přispěvatelé: 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
Rok vydání: 2021
Předmět:
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
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 3
International Journal of Molecular Sciences, Vol 22, Iss 1076, p 1076 (2021)
DOI: 10.17863/cam.63742
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: