SFEBES2021 Poster Presentations Neuroendocrinology and Pituitary (47 abstracts)
Cabergoline treatment in human primary non-functioning pituitary adenomas
Federica Begalli 1 , Tatsuya Komagata 2 , Oniz Suleyman 1 , Kesson Magid 1 , Thomas Rice 1 , David Collier 1 , Neil Dorward 3 , Joan Grieve 3 , Nigel Mendoza 4 , Ramesh Nair 4 , Angelos Kolias 3 , Danyal Khan 3 , Hani J Marcus 3 , Joaquin Botta 1 , Peter J McCormick 1 , Koji Shinozaki 2 & Márta Korbonits 1
1 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; 2Ono Pharmaceutical Co., Ltd, Osaka, Japan; 3UCL Queen Square Institute of Neurology, London, United Kingdom; 4Charing Cross Hospital, London, United Kingdom
Non-functioning pituitary adenomas (NFPAs) are the second most common subtype (15-43%) of all clinically presenting pituitary adenomas. Although the primary treatment of symptomatic NFPAs is surgery, gross total resection is achieved only in about 66% of the cases, and 20% of gross total resected tumours recur after 10 years. Despite recent advances in medical management of pituitary tumours, NFPAs remain the only subtype with no widely accepted pharmacological treatment. Expression of dopamine receptor type 2 (DRD2) in NFPAs suggests dopamine agonists as a potential treatment strategy. The DRD2 agonist cabergoline is already used as first-line treatment of prolactinomas to induce tumour shrinkage and reduce prolactin secretion. Here we aim to investigate the efficacy of cabergoline on human NFPA tissue. We assessed DRD2 expression levels via immunohistochemistry and qPCR in a large cohort of NFPAs (n = 40) and in few prolactinomas. Two different DRD2 isoforms, long (D2RL) and short (D2RS), are differently expressed, and cell viability varied according to subtype. In cabergoline-sensitive prolactinomas D2RS is the predominant isoform, while in NFPAs the D2RS shows similar expression levels to D2RL. In NFPAs we observed a significant decrease of cAMP production after cabergoline treatment (45% ±7; P <0.0001); however, viability after one-week cabergoline treatment showed only 4% (±0.7; P < 0.0002) reduction, compared to a 20% decrease in prolactinomas. Our data suggest that the difference in cabergoline responses between NFPAs and prolactinomas may be due to their distinct expression of D2DR isoforms. These isoforms differ by 29 amino acids in the third cytoplasmic loop, essential for G-protein binding. It has been shown that D2RL, but not D2RS, requires Gai2. The difference in D2R isoform expression could translate to distinct G-protein activation, ultimately leading to the contrasting viability results after cabergoline treatment. Taken together, these data will help inform future treatment strategies for patients with NFPAs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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