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Leo J Hofland - One of the best experts on this subject based on the ideXlab platform.
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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
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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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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 and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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 sst5 mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH Release in a dose-dependent manner with an IC50 value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH Release inhibition (IC50, 0.5 nm), compared with OCT (IC50, 0.02 nm) and SRIF-14 (IC50, 0.02 nm). A positive correlation was found between sst2 but...
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relative potencies of the somatostatin analogs octreotide bim 23014 and rc 160 on the inhibition of Hormone Release by cultured human endocrine tumor cells and normal rat anterior pituitary cells
Endocrinology, 1994Co-Authors: Leo J Hofland, M. Waaijers, J. Zuyderwijk, P. M. Van Koetsveld, S. W. J. LambertsAbstract:In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH Release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin Release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or a-subunit Release by human GH-secreting pituitary adenoma cells in concentrations as low as 10-‘2-10-14 M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH Release (P < 0.01, RC-160 us. octreotide and BIM-23014). In rat-anterior pituitary cell cultures, the IC,, values for inhibition of GH Release were. in rank order of potency, 0.1, 5.3, 47, 48, and 99 PM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH Release bv rat anterior pituitary cells in uitro. Forskolin (100 $4) as well as pretreatment of the ce1G with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data siggest that octreotide, RC-160, and BIM23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin Release significantly more than octreotide at lo-“- and 10-14-M concentrations-(P < O.Oi). In conclusion. the SS analogs octreotide. RC-160. and BIM-23014 may have significant different potencies bf inhibition of Hormone Release in u&o, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors. (Endocrinology 134: 301306,1994)
Michael Horowitz - One of the best experts on this subject based on the ideXlab platform.
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effects of intraduodenal lipid and protein on gut motility and Hormone Release glycemia appetite and energy intake in lean men
The American Journal of Clinical Nutrition, 2013Co-Authors: Amy T Ryan, Michael Horowitz, Natalie D Luscombemarsh, Alexander A Saies, Tanya J Little, Scott Standfield, Christine FeinlebissetAbstract:Background: Intraduodenal lipid modulates gastrointestinal motility and Hormone Release and suppresses energy intake (EI) more than does intraduodenal glucose. Oral protein is the most satiating macronutrient and modulates postprandial glycemia; the comparative effects of intraduodenal protein and lipid and their combined effects are unclear. Objective: We investigated the effects of intraduodenal protein and lipid, alone or in combination, on antropyloroduodenal motility, gastrointestinal Hormone Release, glycemia, and EI. Design: Twenty lean men were studied on 5 randomized, doubleblind occasions. Antropyloroduodenal motility, cholecystokinin, glucagonlike peptide-1 (GLP-1), insulin, glucagon, blood glucose, appetite, and nausea were measured during 90-min isocaloric (3 kcal/min) intraduodenal infusions of lipid [pure lipid condition (L3)], protein [pure protein condition (P3)], a 2:1 combination of lipid and protein [2:1 lipid:protein condition (L2P1)], a 1:2 combination of lipid and protein [1:2 lipid:protein condition (L1P2)], or a control. Immediately after the infusion, EI from a buffet lunch was quantified. Results: In comparison with the control, all nutrient infusions suppressed antral and duodenal and stimulated pyloric pressures (P , 0.05). Cholecystokinin and GLP-1 Release and pyloric stimulation were lipid-load dependent (r $ 0.39, P , 0.01), insulin and glucagon Releases were protein-load dependent (r = 0.83, P , 0.001), and normoglycemia was maintained. L3 but not P3 increased nausea (P , 0.05). Compared with the control, L3 and P3 but not L2P1 or L1P2 suppressed EI (P , 0.05) without major effects on appetite. Conclusions: In lean men, despite differing effects on gut function, intraduodenal lipid and protein produce comparable reductions in energy intake. The effects of lipid may be a result of nausea. Protein also regulates blood glucose by stimulating insulin and glucagon. In contrast, at the loads selected, lipid:protein combinations did not suppress energy intake, suggesting that a threshold load is required to elicit effects. This trial was registered at Australia and New Zealand Clinical Trial Registry (http://www.anzctr.org.au) as 12609000949280. Am J Clin Nutr doi: 10.3945/ajcn.113.061333.
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intraduodenal protein modulates antropyloroduodenal motility Hormone Release glycemia appetite and energy intake in lean men
The American Journal of Clinical Nutrition, 2012Co-Authors: Amy T Ryan, Michael Horowitz, Judith M. Wishart, Christine Feinlebisset, Asimina Kallas, Peter M Clifton, Natalie D LuscombemarshAbstract:BACKGROUND Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and Hormone Release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. OBJECTIVE We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal Hormone Release, glucose and insulin concentrations, appetite perceptions, and energy intake. DESIGN Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. RESULTS Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = -0.51, P < 0.001). CONCLUSION The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal Hormone Release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044.
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load dependent effects of duodenal glucose on glycemia gastrointestinal Hormones antropyloroduodenal motility and energy intake in healthy men
American Journal of Physiology-endocrinology and Metabolism, 2007Co-Authors: Amelia N Pilichiewicz, Michael Horowitz, André J. P. M. Smout, Judith M. Wishart, Reawika Chaikomin, Ixchel M Brennan, Christopher K Rayner, Karen L Jones, Christine FeinlebissetAbstract:Gastric emptying is a major determinant of glycemia, gastrointestinal Hormone Release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glu...
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Original contributionEffect of small intestinal nutrient infusion on appetite, gastrointestinal Hormone Release, and gastric myoelectrical activity in young and older men
The American Journal of Gastroenterology, 2001Co-Authors: Caroline G. Macintosh, Michael Horowitz, Marc A.m.t. Verhagen, André J. P. M. Smout, Judith M. Wishart, Howard A. Morris, Elizabeth A. Goble, John E. Morley, Ian ChapmanAbstract:OBJECTIVE: The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI Hormone Release, and gastric myoelectrical activity. METHODS: Thirteen older (65–84 yr) and 13 young (18–32 yr) healthy men received isovolumetric, intraduodenal (ID) infusions of saline (control), lipid, and glucose for 120 min, on separate days. The energy content of the lipid and glucose infusions was identical at 2.86 kcal/min. Immediately after the ID infusions, each subject was offered a buffet meal, and ad libitum food intake was quantified. Blood glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide were measured. Gastric myoelectrical activity was measured by surface electrogastrography (EGG). RESULTS: ID lipid suppressed food intake in both the young and older men (p < 0.05), whereas ID glucose suppressed food intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin (p < 0.05) responses to ID glucose were greater in older than young men. However, there were no differences in glucagon-like peptide 1 or glucose-dependent insulinotropic peptide responses to any of the infusions. There was a greater increase in the EGG power ratio both during and after ID glucose infusion in the young (p < 0.05) than the older men, and an attenuation of EGG frequency by nutrient infusions in older, but not young, men. CONCLUSIONS: Our findings indicate that aging is associated with nutrient-specific changes in appetite, hormonal, and gastric myoelectrical (EGG) responses to ID nutrients. An enhanced satiating effect of small intestinal carbohydrates may potentially contribute to the anorexia of aging.
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effect of small intestinal nutrient infusion on appetite gastrointestinal Hormone Release and gastric myoelectrical activity in young and older men
The American Journal of Gastroenterology, 2001Co-Authors: Caroline G. Macintosh, Michael Horowitz, Marc A.m.t. Verhagen, André J. P. M. Smout, Judith M. Wishart, Howard A. Morris, Elizabeth A. Goble, John E. Morley, Ian T ChapmanAbstract:Effect of small intestinal nutrient infusion on appetite, gastrointestinal Hormone Release, and gastric myoelectrical activity in young and older men
P. M. Van Koetsveld - One of the best experts on this subject based on the ideXlab platform.
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Dissociation between the Effects of Somatostatin (SS) and Octapeptide SS-Analogs on Hormone Release in a Small Subgroup of Pituitary- and Islet Cell Tumors
2016Co-Authors: Lj Hofland, W. W. De Herder, J. Zuyderwijk, H. A. Visser-wisselaar, C. Van Uffelen, M. Waaijers, P. Uitterlinden, M. J. M. Kros, P. M. Van Koetsveld, S. W. J. LambertsAbstract:The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on Hormone Release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolacti-nomas, and 2 insulinomas were investigated. In the pituitary ade-noma cultures, a comparison was made with the effects of the dopa-mine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) ex-pression was determined by ligand binding studies and by in situ hybridization to detect sst1, sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of a-subunit, FSH, and/or LH. In the other cultures, Hormone and/or subunit re-lease was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM
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Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Dissociation between the Effects of Somatostatin (SS) and Octapeptide SS-Analogs on Hormone Release in a Small Subgroup of Pituitary- and Isl
2013Co-Authors: Lj Hofland, W. W. De Herder, J. Zuyderwijk, H. A. Visser-wisselaar, C. Van Uffelen, M. Waaijers, P. Uitterlinden, M. J. M. Kros, P. M. Van Koetsveld, S. W. J. LambertsAbstract:The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on Hormone Release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the pituitary adenoma cultures, a comparison was made with the effects of the dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was determined by ligand binding studies and by in situ hybridization to detect sst 1, sst 2, and sst 3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of �-subunit, FSH, and/or LH. In the other cultures, Hormone and/or subunit Release was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM
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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
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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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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 and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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 sst5 mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH Release in a dose-dependent manner with an IC50 value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH Release inhibition (IC50, 0.5 nm), compared with OCT (IC50, 0.02 nm) and SRIF-14 (IC50, 0.02 nm). A positive correlation was found between sst2 but...
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relative potencies of the somatostatin analogs octreotide bim 23014 and rc 160 on the inhibition of Hormone Release by cultured human endocrine tumor cells and normal rat anterior pituitary cells
Endocrinology, 1994Co-Authors: Leo J Hofland, M. Waaijers, J. Zuyderwijk, P. M. Van Koetsveld, S. W. J. LambertsAbstract:In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH Release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin Release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or a-subunit Release by human GH-secreting pituitary adenoma cells in concentrations as low as 10-‘2-10-14 M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH Release (P < 0.01, RC-160 us. octreotide and BIM-23014). In rat-anterior pituitary cell cultures, the IC,, values for inhibition of GH Release were. in rank order of potency, 0.1, 5.3, 47, 48, and 99 PM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH Release bv rat anterior pituitary cells in uitro. Forskolin (100 $4) as well as pretreatment of the ce1G with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data siggest that octreotide, RC-160, and BIM23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin Release significantly more than octreotide at lo-“- and 10-14-M concentrations-(P < O.Oi). In conclusion. the SS analogs octreotide. RC-160. and BIM-23014 may have significant different potencies bf inhibition of Hormone Release in u&o, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors. (Endocrinology 134: 301306,1994)
M. Waaijers - One of the best experts on this subject based on the ideXlab platform.
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Dissociation between the Effects of Somatostatin (SS) and Octapeptide SS-Analogs on Hormone Release in a Small Subgroup of Pituitary- and Islet Cell Tumors
2016Co-Authors: Lj Hofland, W. W. De Herder, J. Zuyderwijk, H. A. Visser-wisselaar, C. Van Uffelen, M. Waaijers, P. Uitterlinden, M. J. M. Kros, P. M. Van Koetsveld, S. W. J. LambertsAbstract:The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on Hormone Release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolacti-nomas, and 2 insulinomas were investigated. In the pituitary ade-noma cultures, a comparison was made with the effects of the dopa-mine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) ex-pression was determined by ligand binding studies and by in situ hybridization to detect sst1, sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of a-subunit, FSH, and/or LH. In the other cultures, Hormone and/or subunit re-lease was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM
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Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Dissociation between the Effects of Somatostatin (SS) and Octapeptide SS-Analogs on Hormone Release in a Small Subgroup of Pituitary- and Isl
2013Co-Authors: Lj Hofland, W. W. De Herder, J. Zuyderwijk, H. A. Visser-wisselaar, C. Van Uffelen, M. Waaijers, P. Uitterlinden, M. J. M. Kros, P. M. Van Koetsveld, S. W. J. LambertsAbstract:The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on Hormone Release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the pituitary adenoma cultures, a comparison was made with the effects of the dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was determined by ligand binding studies and by in situ hybridization to detect sst 1, sst 2, and sst 3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of �-subunit, FSH, and/or LH. In the other cultures, Hormone and/or subunit Release was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM
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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
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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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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 and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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 sst5 mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH Release in a dose-dependent manner with an IC50 value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH Release inhibition (IC50, 0.5 nm), compared with OCT (IC50, 0.02 nm) and SRIF-14 (IC50, 0.02 nm). A positive correlation was found between sst2 but...
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relative potencies of the somatostatin analogs octreotide bim 23014 and rc 160 on the inhibition of Hormone Release by cultured human endocrine tumor cells and normal rat anterior pituitary cells
Endocrinology, 1994Co-Authors: Leo J Hofland, M. Waaijers, J. Zuyderwijk, P. M. Van Koetsveld, S. W. J. LambertsAbstract:In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH Release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin Release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or a-subunit Release by human GH-secreting pituitary adenoma cells in concentrations as low as 10-‘2-10-14 M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH Release (P < 0.01, RC-160 us. octreotide and BIM-23014). In rat-anterior pituitary cell cultures, the IC,, values for inhibition of GH Release were. in rank order of potency, 0.1, 5.3, 47, 48, and 99 PM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH Release bv rat anterior pituitary cells in uitro. Forskolin (100 $4) as well as pretreatment of the ce1G with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data siggest that octreotide, RC-160, and BIM23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin Release significantly more than octreotide at lo-“- and 10-14-M concentrations-(P < O.Oi). In conclusion. the SS analogs octreotide. RC-160. and BIM-23014 may have significant different potencies bf inhibition of Hormone Release in u&o, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors. (Endocrinology 134: 301306,1994)
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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
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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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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 and Metabolism, 2004Co-Authors: Leo J Hofland, M. Waaijers, P. M. Van Koetsveld, Joost Van Der Hoek, Wouter W De Herder, Diana Sprijmooij, Christian Bruns, Gisbert Weckbecker, Richard A Feelders, Aartjan Van Der LelyAbstract: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 sst5 mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH Release in a dose-dependent manner with an IC50 value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH Release inhibition (IC50, 0.5 nm), compared with OCT (IC50, 0.02 nm) and SRIF-14 (IC50, 0.02 nm). A positive correlation was found between sst2 but...