Context. Cortistatin (CST) is a neuropeptide, which shares high homology with somatostatin and binds with high affinity to all somatostatin receptor (SSTR) subtypes. Many of its endocrine and biological activities overlap with those of stomatostatin.

Objective/Design. To assess the direct in vitro effects of CST on human pituitary hormone secretion.

Setting. This study was performed in the Endocrine laboratory of a tertiary academic medical center.

Materials. Primary cell cultures of human fetal (21-25 weeks’ gestation) pituitary tissues and cultured hormone-secreting adenoma cells.

Interventions. Incubation with CST-14 or CST-17, somatostatin, growth hormone- releasing hormone (GHRH), and SSRT- and ghrelin analogs.

Outcome measures. Growth hormone (GH) and prolactin (PRL) medium concentrations, tested by hormone assay; SSTRs mRNA, tested by RT-PCR.

Results. CST-14 (10 nM) inhibited GH secretion by up to 65% in all fetal pituitary specimens after 4-h incubation (P < 0.05). CST-14 or CST-17 (10 nM) inhibited basal GH secretion in 6 of the 13 GH-cell adenomas and 2 of the 3 GH-PRL mixed adenomas. CST-17 (100 nM) suppressed the GH response to GHRH and ghrelin analog (10 nM each) by 30-50% in adenomas (P < 0.05). Three PRL-adenomas treated with CST-17 (10 nM) showed a 20-40% inhibition of PRL release (P < 0.05), whereas in three others no suppression or mild response was achieved at this concentration. A comparable inhibition of PRL secretion was obtained with SSTR5-selective analog but significantly less with SSTR2-preferential compounds.

RT-PCR revealed the expression of both SSTR2 and SSTR5 receptors in all GH-cell and mixed adenomas studied and in all PRL-secreting adenomas studied, except for two of the CST-resistant prolactinomas, in which SSTR5 was absent.

Conclusion. This is the first report of in vitro CST suppression of human GH and PRL in cultured pituitary tissues. The regulation of PRL release from cultured adenomas appears to be primarily mediated by SSTR5.