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Natriuretic peptide expression and function in GH3 somatolactotropes and feline somatotrope pituitary tumors

Mirczuk, Samantha; Scudder, Christopher; Read, Jordan; Crossley, Victoria; Regan, Jacob; Richardson, Karen; Simbi, Bigboy; Mcardle, Craig; Church, David; Fenn, Joseph; Kenny, Patrick; Volk, Holger; Wheeler-Jones, Caroline; Korbonits, Márta; Niessen, Stijn; Mcgonnell, Imelda; Fowkes, Robert


Samantha Mirczuk

Christopher Scudder

Jordan Read

Victoria Crossley

Jacob Regan

Karen Richardson

Bigboy Simbi

Craig Mcardle

David Church

Joseph Fenn

Patrick Kenny

Holger Volk

Caroline Wheeler-Jones

Márta Korbonits

Stijn Niessen

Imelda Mcgonnell

Robert Fowkes


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 100nM TRH or 10µM 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. Estrogen 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.


Mirczuk, S., Scudder, C., Read, J., Crossley, V., Regan, J., Richardson, K., …Fowkes, R. (2021). Natriuretic peptide expression and function in GH3 somatolactotropes and feline somatotrope pituitary tumors. International Journal of Molecular Sciences, -.

Journal Article Type Article
Acceptance Date Jan 20, 2021
Online Publication Date Jan 22, 2021
Publication Date Jan 22, 2021
Deposit Date Dec 26, 2020
Publicly Available Date Feb 22, 2021
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
Peer Reviewed Peer Reviewed
Pages -
Keywords CNP; multiplex RT-qPCR; pituitary; somatotrope; acromegaly; feline
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