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Somatostatin Receptor Subtype 1 Selective Activation in Human Growth Hormone (GH)- and Prolactin (PRL)-Secreting Pituitary Adenomas: Effects on Cell Viability, GH, and PRL Secretion

Section of Endocrinology (M.C.Z., D.P., F.T., M.R.A., A.M., E.C.d.U.), Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, 44100 Ferrara, Italy; Division of Neurosurgery (R.P.), Hospital of Ferrara, 44100 Ferrara, Italy; Division of Neurosurgery (M.S.), Hospital of Padova, 35100 Padova, Italy; and Biomeasure Inc./Beaufour-IPSEN (M.D.C.), Milford, Massachusetts 01757-3650

Address all correspondence and requests for reprints to: Ettore C. degli Uberti, M.D., Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy. E-mail: ti8{at}dns.unife.it.

Somatostatin (SRIF) analogs interacting with SRIF receptor subtype (SSTR) 2 and SSTR5 are known to reduce secretion in GH-secreting pituitary adenomas. We investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH and prolactin (PRL) secretion and cell viability in primary cultures deriving from 15 GH- and PRL-secreting adenomas expressing SSTR1. Quantitative RT-PCR showed SSTR1 mRNA mean levels of 6 ± 2.2 x 10⁴ molecules/µg reverse-transcribed total RNA. SSTR2 and SSTR5 were frequently expressed (93.3%), on the contrary of SSTR3 (53.3%) and SSTR4 (6.7%). GH secretion was significantly reduced by SRIF and BIM-23926 (45 ± 8.6% and 32 ± 18.1% inhibition, respectively) as well as PRL secretion (16.1 ± 4% and 19.7 ± 3.5% inhibition, respectively). After treatment with SRIF and BIM-23926, cell viability was significantly reduced by 17.5 ± 5% and 20 ± 3.9%, respectively. SSTR1 mRNA levels correlated with the degree of GH and PRL secretion inhibition. These results demonstrate that SSTR1 selective activation inhibits hormone secretion and cell viability in GH- and PRL-secreting adenomas in vitro and suggest that SRIF analogs with affinity for SSTR1 may be useful to control hormone hypersecretion and reduce neoplastic growth of pituitary adenomas.

This work was supported by grants from the Italian Ministry of University and Scientific and Technological Research (60%, 2001; MIUR 2002067251-003), Fondazione Cassa di Risparmio di Ferrara, IPSEN S.p.A. (Milano, Italy), and the Associazione Ferrarese dell’Ipertensione Arteriosa.

Abbreviations: IRMA, Immunoradiometric assay; PRL, prolactin; QPCR, quantitative PCR; RT, reverse transcription; SRIF, somatostatin; SSTR, SRIF receptor subtype.

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