Submitted on March 20, 2007
Accepted on September 10, 2007
Modulation of expression of somatostatin receptor subtypes in Graves' ophthalmopathy orbits: relevance to novel analogues
Irina Cozma1, Lei Zhang2, James M Uddin3, Carol M Lane4, Aled Rees2, and Marianne Ludgate2*
1 CEDS and Ophthalmology, Cardiff University, United Kingdom
2 CEDS, Cardiff University, United Kingdom
3 Moorfield's Eye Hospital, University of London, United Kingdom
4 Ophthalmology, Cardiff University, United Kingdom
* To whom correspondence should be addressed. E-mail: ludgate{at}cf.ac.uk.
Apart from evaluating orbital inflammation in Graves' ophthalmopathy (GO) somatostatin (SST) analogues have been proposed as a therapy but recent trials were disappointing. We aimed to measure somatostatin receptor (SSTR) expression in orbital tissues ex vivo and determine whether the new broad-affinity analogue SOM230 might be of therapeutic use.
Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analysed. Transcripts were quantified using SYBR-green and a light cycler. In vitro models were used to investigate whether thyrotropin receptor activation (as occurs via thyroid stimulating antibodies) or adipogenesis affected SSTR expression in primary preadipocytes and to compare the biological activity of octreotide and SOM230 in their modulation.
The expression of SSTR1 was significantly higher in GO patients than normal controls (p=0.024). Although differences in the expression of SSTR2 were not significant, 39% of GO samples had levels above the 97th centile of the controls. SSTR3, 4 & 5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3-
transcripts were at the LOD. TSHR activation did not modulate SSTR expression. An in vitro model of adipogenesis indicated upregulation of SSTR1 and SSTR2 during differentiation. SOM230 produced significantly greater inhibition of orbital preadipocyte proliferation than octreotide.
Ex vivo analysis of orbital tissues reveals upregulation of SSTR1 & 2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase.
