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Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

Financial support for medical editorial assistance was provided by Novartis Pharma AG. We thank Ray Hill, an independent medical writer who provided English-language editing and journal styling prior to submission on behalf of Springer Healthcare Communications.

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Authors and Affiliations

  1. Endocrinology Unit, Department of Internal Medicine, Policlinico San Martino, 16132, Genoa, Italy

    Federico Gatto, Massimo Giusti, Mara Boschetti & Diego Ferone

  2. University of Genoa, Genoa, Italy

    Marica Arvigo, Jessica Amarù, Claudia Campana, Francesco Cocchiara, Giulia Graziani, Eleonora Bruzzone, Massimo Giusti, Mara Boschetti & Diego Ferone

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  1. Federico Gatto
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Correspondence to Federico Gatto.

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FG has been a speaker for Novartis and has participated on advisory boards of Novartis, AMCo Ltd, and IONIS Pharmaceuticals. DF has been a speaker for and participated on advisory boards and received research grants from Novartis, Ipsen and Pfizer. The other Authors have no conflicts of interest to declare.

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Gatto, F., Arvigo, M., Amarù, J. et al. Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells. Pituitary 22, 89–99 (2019). https://doi.org/10.1007/s11102-018-0926-y

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