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

International Journal of Molecular Sciences

Márta Korbonits¹  PatrickJ. Kenny²  DavidB. Church²  Joseph Fenn²  HolgerA. Volk²  StijnJ. Niessen²  Bigboy Simbi³  ImeldaM. McGonnell³  CarolineP. Wheeler-Jones³  CraigA. McArdle⁴  RobertC. Fowkes⁵  SamanthaM. Mirczuk⁵  KarenM. Richardson⁵  JacobT. Regan⁵  VictoriaJ. Crossley⁵  JordanE. Read⁵  ChristopherJ. Scudder⁵ 

[1] Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK;Clinical Sciences & Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK;Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK;Department of Translational Science, Bristol Medical School, University of Bristol, Whitson Street, Bristol BS1 3NY, UK;Endocrine Signalling Group, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK;

关键词: CNP;    multiplex RT-qPCR;    pituitary;    somatotrope;    acromegaly;    feline;   

DOI  :  10.3390/ijms22031076

来源: DOAJ

【 摘 要 】

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 µM 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.

【 授权许可】

Unknown