کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2802542 1156687 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues — Observations in two patients with acromegaly and severe headache
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues — Observations in two patients with acromegaly and severe headache
چکیده انگلیسی


• Treatment of acromegaly is based on surgery or/and somatostatin analogues.
• We examined expression of somatostatin receptors 1–5 in two acromegaly patients.
• Highly expressed truncated receptor 5 (sst5TMD4) influenced treatment result.
• Sst5TMD4 has dominant-negative effect on somatostatin receptor 2 signaling pathways.

BackgroundSomatotropinomas have unique “fingerprints” of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown.Patients and methodsWe investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas.ResultsCase 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA. Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50–75% and sst5 in 75–100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20–57% of tumor cells.ConclusionsA poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Growth Hormone & IGF Research - Volume 25, Issue 5, October 2015, Pages 262–267
نویسندگان
, , , , , , ,