Endocrine Abstracts

Pituitary adenomas (PA) comprise a commonly underestimated pathology in terms of incidence and associated morbimortality. Somatostatin and dopamine analogs constitute the main medical treatment for PA. However, an appreciable subset of patients are resistant or poorly responsive to these drugs, and hence, the search for new therapies to control tumor growth and/or hormone secretion is crucial. Biguanides such as metformin (MF; commonly used to treat type-2 diabetes), phenformin (PF) and buformin (BF) have been shown to exert antitumor actions in different tumor types, but their actions in PA cells have not been reported. The aim of this study was to determine the effect of these biguanides on key functional parameters (i.e. cell viability, hormone secretion, calcium signaling) in human PA cell cultures: 7 corticotropinomas (ACTHomas), 5 somatotropinomas (GHomas), and 3 non-functioning PA (NFPAs). Expression profile of somatostatin (ssts) and dopamine receptors (DRs) showed typical receptor profiles for each pathologies (ACTHomas: sst5>sst2>sst1; GHomas: sst5≥sst2; NFPAs: sst3≥sst2; and DR2 was the most abundant DR in all these PAs). Interestingly, MF moderately, albeit consistently reduced cell viability in PA cells, while treatment with PF and BF reduced cell viability more noticeably, with the effect of PF very particularly intense in ACTHomas. These effects might involve a calcium-dependent mechanism, since treatment with these biguanides clearly altered the kinetics of cytosolic free calcium. Finally, MF and BF showed a non-significant trend to reduce ACTH secretion in corticotropinomas, whereas, in primary pituitary cell culture of two primate species, MF significantly decreased ACTH and GH release. Taken together, our results reveal a clear inhibitory effect of biguanides on PA cell viability in vitro, and given their demonstrated clinical safety suggest a potential therapeutic role of these compounds for the treatment of patients PAs.