Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells
| Autor: | Federico Gatto, Massimo Giusti, Mara Boschetti, Eleonora Bruzzone, Francesco Cocchiara, Marica Arvigo, Diego Ferone, Giulia Graziani, Jessica Amarù, Claudia Campana |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Agonist
endocrine system Adenoma Somatotropic cell medicine.drug_class Endocrinology Diabetes and Metabolism Octreotide 030209 endocrinology & metabolism Primary cultures 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Adrenocorticotropic Hormone Acromegaly medicine Animals Humans ACTH-secreting Receptors Somatostatin Corticotrophs Cells Cultured Pituitary adenomas Somatostatin receptor business.industry GH-secreting Pasireotide medicine.disease Somatotrophs Diabetes and Metabolism Somatostatin chemistry Pituitary Gland Cancer research business 030217 neurology & neurosurgery medicine.drug |
| Popis: | Pasireotide is a second-generation somatostatin (SRIF) receptor ligand (SRL), approved for medical treatment of acromegaly and Cushing’s disease (CD). The molecule is a stable cyclohexapeptide synthetized based on SRIF structure. Differently from first-generation SRLs (e.g. octreotide), preferentially binding somatostatin receptor (SST) subtype 2 (SST2), pasireotide has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Interestingly, early preclinical studies demonstrated that pasireotide shows distinct functional properties compared to SRIF and first-generation SRLs when binding SSTs. We aimed to highlight the differential receptor-targeted action of pasireotide in the treatment of somatotroph and corticotroph adenomas, throughout the critical revision of preclinical studies carried out on acromegaly and CD models. Different authors demonstrated that the antisecretory effect of pasireotide in somatotroph adenoma cell cultures is comparable to that of the SST2-preferential agonist octreotide. Some reports even show a direct correlation between SST2 mRNA expression and GH reduction after pasireotide treatment, thus laying for a predominant role of SST2 in driving pasireotide efficacy in somatotropinomas in vitro. On the other hand, the inhibitory effect of pasireotide on ACTH secretion in corticotropinoma cells seems to be mainly mediated by SST5. Indeed, most reports show a higher potency and efficacy of pasireotide compared to SST2 preferential agonists, while functional studies confirm the pivotal role of SST5 targeting in corticotroph cells. The analysis of preclinical studies carried out in somatotroph and corticoph adenomas points out that pasireotide shows a cell-specific activity, exerting its biological effects via different SSTs in the different adenoma histotypes. |
| Databáze: | OpenAIRE |
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