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Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs
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| Zeitschriftentitel: | American Journal of Physiology-Endocrinology and Metabolism |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | American Journal of Physiology-Endocrinology and Metabolism, 293, 2007, 6, S. E1630-E1635 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
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| Schlagwörter: |
| author_facet |
Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian |
|---|---|
| author |
Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian |
| spellingShingle |
Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian American Journal of Physiology-Endocrinology and Metabolism Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism |
| author_sort |
cozma, irina |
| spelling |
Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian 0193-1849 1522-1555 American Physiological Society Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism http://dx.doi.org/10.1152/ajpendo.00177.2007 <jats:p> Apart from evaluating orbital inflammation in Graves’ ophthalmopathy (GO), somatostatin (SST) analogs 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 analog SOM230 might be of therapeutic use. Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analyzed. 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 percentile of the controls. SSTR3, -4, and -5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3α transcripts were at the LOD. TSH receptor 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 and -2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. </jats:p> Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs American Journal of Physiology-Endocrinology and Metabolism |
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| title |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_unstemmed |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_full |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_fullStr |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_full_unstemmed |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_short |
Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_sort |
modulation of expression of somatostatin receptor subtypes in graves’ ophthalmopathy orbits: relevance to novel analogs |
| topic |
Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism |
| url |
http://dx.doi.org/10.1152/ajpendo.00177.2007 |
| publishDate |
2007 |
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E1630-E1635 |
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<jats:p> Apart from evaluating orbital inflammation in Graves’ ophthalmopathy (GO), somatostatin (SST) analogs 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 analog SOM230 might be of therapeutic use. Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analyzed. 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 percentile of the controls. SSTR3, -4, and -5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3α transcripts were at the LOD. TSH receptor 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 and -2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. </jats:p> |
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| author | Cozma, Irina, Zhang, Lei, Uddin, James, Lane, Carol, Rees, Aled, Ludgate, Marian |
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| description | <jats:p> Apart from evaluating orbital inflammation in Graves’ ophthalmopathy (GO), somatostatin (SST) analogs 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 analog SOM230 might be of therapeutic use. Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analyzed. 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 percentile of the controls. SSTR3, -4, and -5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3α transcripts were at the LOD. TSH receptor 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 and -2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. </jats:p> |
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| spelling | Cozma, Irina Zhang, Lei Uddin, James Lane, Carol Rees, Aled Ludgate, Marian 0193-1849 1522-1555 American Physiological Society Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism http://dx.doi.org/10.1152/ajpendo.00177.2007 <jats:p> Apart from evaluating orbital inflammation in Graves’ ophthalmopathy (GO), somatostatin (SST) analogs 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 analog SOM230 might be of therapeutic use. Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analyzed. 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 percentile of the controls. SSTR3, -4, and -5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3α transcripts were at the LOD. TSH receptor 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 and -2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. </jats:p> Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs American Journal of Physiology-Endocrinology and Metabolism |
| spellingShingle | Cozma, Irina, Zhang, Lei, Uddin, James, Lane, Carol, Rees, Aled, Ludgate, Marian, American Journal of Physiology-Endocrinology and Metabolism, Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs, Physiology (medical), Physiology, Endocrinology, Diabetes and Metabolism |
| title | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_full | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_fullStr | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_full_unstemmed | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_short | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_sort | modulation of expression of somatostatin receptor subtypes in graves’ ophthalmopathy orbits: relevance to novel analogs |
| title_unstemmed | Modulation of expression of somatostatin receptor subtypes in Graves’ ophthalmopathy orbits: relevance to novel analogs |
| topic | Physiology (medical), Physiology, Endocrinology, Diabetes and Metabolism |
| url | http://dx.doi.org/10.1152/ajpendo.00177.2007 |