DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours.

Abstract

OBJECTIVE:

Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin-suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide.

METHODS:

Twenty-seven hSA were characterised immunohistochemically for their hormone- and sst-expression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time- (n=6) and dose-response (n=21) experiments. A positive response was defined as GH suppression to below 80% of baseline.

RESULTS:

In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC(50) were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (n=6) nor tumour morphology was related to the GH response. However, semi-quantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression.

CONCLUSIONS:

DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide.

• Authors: U Plöckinger, U Hoffmann, M Geese, A Lupp, M Buchfelder, J Flitsch, P Vajkoczy, W Jakob, W Saeger, S Schulz, C Dohrmann
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 166 Issue 2 Pg. 223-34 (Feb 2012) ISSN: 1479-683X [Electronic] England
• PMID: 22065857 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Oligopeptides
• PTR 3173
• Receptors, Somatostatin
• somatostatin receptor subtype-4
• Human Growth Hormone
• Somatostatin
• somatostatin receptor 5
• somatostatin receptor 2
• Octreotide

Topics

• Adenoma (drug therapy, metabolism, pathology, surgery)
• Adult
• Aged
• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Down-Regulation (drug effects)
• Drug Evaluation, Preclinical
• Drug Resistance, Neoplasm (drug effects)
• Female
• Growth Hormone-Secreting Pituitary Adenoma (drug therapy, metabolism, pathology, surgery)
• Human Growth Hormone (metabolism)
• Humans
• Male
• Middle Aged
• Octreotide (therapeutic use)
• Oligopeptides (pharmacology, therapeutic use)
• Receptors, Somatostatin (agonists)
• Somatostatin (analogs & derivatives, pharmacology)
• Substrate Specificity
• Treatment Outcome
• Tumor Cells, Cultured