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

J Clin Endocrinol Metab. 2003 Jun;88(6):2797-802. doi: 10.1210/jc.2002-021825.

Abstract

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 10(4) molecules/ microg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / physiopathology
  • Adult
  • Cell Survival / drug effects
  • Female
  • Human Growth Hormone / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms / metabolism*
  • Pituitary Neoplasms / physiopathology
  • Prolactin / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / agonists
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Somatostatin / pharmacology

Substances

  • RNA, Messenger
  • Receptors, Somatostatin
  • somatostatin receptor type 1
  • Human Growth Hormone
  • Somatostatin
  • Prolactin