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The Novel Somatostatin Analog SOM230 Is a Potent Inhibitor of Hormone Release by Growth Hormone- and Prolactin-Secreting Pituitary Adenomas in Vitro
Open accessAbstract
To determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenomas. OCT (10 nM) significantly inhibited GH release in seven of nine GH-secreting pituitary adenoma cultures (range, -26 to -73%), SOM230 (10 nM) in eight of nine cultures (range, -22 to -68%), and SRIF-14 (10 nM) in six of six cultures (range, -30 to -75%). The sst analysis showed predominant but variable levels of somatostatin receptor (sst)(2) and sst(5) mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH release in a dose-dependent manner with an IC(50) value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH release inhibition (IC(50), 0.5 nM), compared with OCT (IC(50), 0.02 nM) and SRIF-14 (IC(50), 0.02 nM). A positive correlation was found between sst(2) but not sst(5) mRNA levels in the adenoma cells and the inhibitory potency of OCT on GH release in vivo and in vitro, and the effects of SOM230 and SRIF-14 in vitro. In three prolactinoma cultures, 10 nM OCT weakly inhibited prolactin (PRL) release in only one (-28%), whereas 10 nM SOM230 significantly inhibited PRL release in three of three cultures (-23, -51, and -64.0%). The inhibition of PRL release by SOM230 was related to the expression level of sst(5) but not sst(2) mRNA. Several conclusions were reached. First, SOM230 has a broad profile of inhibition of tumoral pituitary hormone release in the low nanomolar range, probably mediated via both sst(2) and sst(5) receptors. The higher number of responders of GH-secreting pituitary adenoma cultures to SOM230, compared with OCT, suggest that SOM230 has the potency to increase the number of acromegalic patients which can be biochemically controlled. Second, compared with OCT, SOM230 is more potent in inhibiting PRL release by mixed GH/PRL-secreting adenoma and prolactinoma cells.
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Dopamine Receptor Expression and Function in Corticotroph Ectopic Tumors
Pivonello, R., Ferone, D., de Herder, W. W., Faggiano, A., Bodei, L., de Krijger, R. R., Lombardi, G., Colao, A., Lamberts, S. W. J., & Hofland, L. J. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0728 · Cited by 68
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Metadata
- Authors
- Hofland, L. J., van der Hoek, J., van Koetsveld, P. M., de Herder, W. W., Waaijers, M., Sprij-Mooij, D., Bruns, C., Weckbecker, G., Feelders, R., van der Lely, A.-J., Beckers, A., & Lamberts, S. W. J.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-04
- Volume
- 89
- Issue
- 4
- Pages
- 1577-1585
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2131231109
- Cited by
- 185
- References
- 0
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hofland, L. J., van der Hoek, J., van Koetsveld, P. M., de Herder, W. W., Waaijers, M., Sprij-Mooij, D., Bruns, C., Weckbecker, G., Feelders, R., van der Lely, A.-J., Beckers, A., & Lamberts, S. W. J. (2004). The Novel Somatostatin Analog SOM230 Is a Potent Inhibitor of Hormone Release by Growth Hormone- and Prolactin-Secreting Pituitary Adenomas in Vitro. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2003-031344
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