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- Title
A novel somatostatin receptor ligand for human ACTH – and GH –secreting pituitary adenomas.
- Authors
Regazzo, Daniela; Avallone, Serena; MacSweeney, Cliona P; Sergeev, Eugenia; Howe, David; Godwood, Alex; Bennett, Kirstie A; Brown, Alastair J H; Barnes, Matt; Occhi, Gianluca; Barbot, Mattia; Faggian, Diego; Tropeano, Maria Pia; Losa, Marco; Lasio, Giovanni; Scaroni, Carla; Giraldi, Francesca Pecori
- Abstract
Objective Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands. Design Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro. Methods Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5 , GH and POMC expression were evaluated after 24 hours. Results HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/ POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTR s expression was detected in all specimens. Conclusions This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly.
- Subjects
ENDOCRINOLOGY; SOMATOSTATIN receptors; ACROMEGALY; CUSHING'S syndrome; TARGET theory (Radiobiology)
- Publication
European Journal of Endocrinology, 2024, Vol 190, Issue 1, pK8
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1093/ejendo/lvad171