Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes

J Clin Endocrinol Metab. 2000 Feb;85(2):781-92. doi: 10.1210/jcem.85.2.6338.


Recently, studies using somatostatin (SRIF) analogs preferential for either the SRIF receptor 2 (SSTR2) or the SSTR5 subtype demonstrated a variable suppression of GH and PRL release from GH-secreting human adenomas. These data suggested the concept of SSTR subtype specificity in such tumors. In the present study the quantitative expression of messenger ribonucleic acid (mRNA) for the 5 SSTR subtypes and the inhibitory effects of SRIF14; SRIF28; octreotide; the SSTR2-preferential analog, BIM-23197; and the SSTR5-preferential analog, BIM-23268, on GH and PRL secretion were analyzed in cells cultured from 15 acromegalic tumors. RT-PCR analysis revealed a consistent pattern of SSTR2 and SSTR5 mRNA expression. SSTR5 mRNA was expressed at a higher level (1052 +/- 405 pg/pg glyceraldehyde-3-phosphate dehydrogenase) than SSTR2 mRNA (100 +/- 30 pg/pg glyceraldehyde-3-phosphate dehydrogenase). However, only SSTR2 mRNA expression correlated with the degree of GH inhibition induced by SRIF14, SRIF28, and BIM-23197. The SSTR5-preferential compound inhibited GH release in only 7 of 15 cases. In cells cultured from the 10 mixed adenomas that secreted both GH and PRL, RT-PCR analysis revealed a consistent coexpression of SSTR5, SSTR2, and SSTR1 mRNA. In all cases SRIF14, SRIF28, and the SSTR5-preferential analog, BIM-23268, significantly suppressed PRL secretion, with a mean maximal inhibition of 48 +/- 4%. In contrast, the SSTR2-preferential analogs, BIM-23197 and octreotide, were effective in suppressing PRL in only 6 of 10 cases. In cells cultured from adenomas taken from patients partially responsive to the SRIF analog, octreotide, partial additivity in suppressing both GH and PRL secretion was observed when the SSTR2- and SSTR5-preferring analogs, BIM-23197 and BIM-23268, were tested in combination. Our data show a highly variable ratio of the SSTR2 and SSTR5 transcripts, according to tumors. The SSTR2-preferring compound consistently inhibits GH release, whereas the SSTR5-preferring compound is the main inhibitor of PRL secretion. When both drugs are combined, the partial additivity observed in mixed GH- plus PRL-secreting adenomas may be of interest in the therapeutic approach of such tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / metabolism*
  • Adenoma / metabolism
  • Adult
  • Cells, Cultured
  • Drug Combinations
  • Female
  • Hormones / pharmacology
  • Human Growth Hormone / antagonists & inhibitors
  • Human Growth Hormone / metabolism
  • Humans
  • Male
  • Middle Aged
  • Octreotide / pharmacology
  • Oligopeptides / pharmacology
  • Phenotype
  • Piperazines / pharmacology
  • Prolactin / antagonists & inhibitors
  • RNA, Messenger / metabolism*
  • Receptors, Somatostatin / agonists
  • Receptors, Somatostatin / genetics
  • Receptors, Somatotropin / genetics*
  • Somatostatin / analogs & derivatives
  • Somatostatin / pharmacology


  • BIM 23197
  • BIM 23268
  • Drug Combinations
  • Hormones
  • Oligopeptides
  • Piperazines
  • RNA, Messenger
  • Receptors, Somatostatin
  • Receptors, Somatotropin
  • somatostatin receptor type 1
  • Human Growth Hormone
  • Somatostatin
  • somatostatin receptor 5
  • Prolactin
  • somatostatin receptor 2
  • Octreotide