30 research outputs found
The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b)
Abstract
The direct effects of human GH and IGF-I on PRL secretion and cell proliferation were studied on PRL secreting rat pituitary tumor 7315b cells in vitro, as well as the effects in vivo of human GH administration on body weight, IGF-I levels and tumor size in rats bearing this transplantable tumor. In the in vitro studies IGF-I levels above 5 nM stimulated PRL release in a dose-dependent manner while GH, in concentrations of 0.23–45 nM, did not affect PRL release. Cell proliferation was stimulated by IGF-I in a dose-dependent manner from 0.5 nM onwards, while GH did not have an effect. The in vivo studies showed that 1 mg GH/rat/day prevented tumor-induced cachexia and normalized the suppressed IGF-I levels without stimulating tumor growth. It is concluded that tumor-induced cachexia can be prevented by exogenous GH administration without an increase in tumor mass, even if a tumor model is used whose cultured tumor cells respond to exposure to IGF-I with a mitotic response
Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors
Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P < 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.</p
Interferon-alpha-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas
Interferon-alpha (IFN alpha) may exert direct inhibitory effects on cell
proliferation and on the production of different peptide hormones. We
investigated the effect of IFN alpha on hormone production by 15
GH-secreting pituitary adenomas, 4 clinically nonfunctioning or
gonadotroph pituitary adenomas, and 4 prolactinomas in vitro. In the
GH-secreting pituitary adenoma cultures, a short term (72-h) incubation
with IFN alpha (50-100 U/mL) significantly inhibited GH secretion in 3 of
7 cases and PRL secretion in 6 of 7 cultures. During prolonged incubation
(14 days) with IFN alpha, GH and/or PRL secretion was significantly
inhibited in 7 of 8 cultures (GH, 17-78% inhibition; PRL, 39-88%
inhibition). In the clinically nonfunctioning or gonadotroph cultures
Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors
Septic shock is the most severe clinical manifestation of meningococcal
disease and is predominantly seen in children under 5 yr of age. Very
limited research has been performed to elucidate the alterations of the
GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis
and the levels of IGF-binding proteins (IGFBPs)
Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors
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 sst1, sst2,
and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete
detectable amounts of alpha-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) in 7 of 11, and by octapeptide SS-analogs
(10 nM) in 3 of 10 cultures. In three NFA cultures, hormone release was
sensitive to SS but not to SS-analogs. In all cultures, except for one,
DA-agonists were the most effective in inhibiting hormone release. In the
prolactinoma cultures, PRL release was inhibited by DA-agonists (10 nM) in
7 of 7, by SS in 4 of 4, and by octapeptide SS-analogs in 3 of 7 cultures.
A dissociation between the effects of SS and SS-analogs was found in 3
cases. In the cultures sensitive to both bromocriptine and SS-28,
bromocriptine was the most potent compound in 2 out of 4 cultures. In the
2 other cultures, both compounds were equally effective. In 2 insulinoma
cultures, insulin release was inhibited by SS, and by octapeptide
SS-analogs in only one. The presence or absence of an inhibitory effect by
octreotide was in all cases in parallel with the presence or absence of
the inhibitory effect by BIM-23014 and RC-160. Autoradiographic studies
using [125I-Tyr0]SS28 showed specific binding in 4 of 5 NFAs, 1 of 2
prolactinomas, and 1 of 1 insulinoma. Specific [125I-Tyr3]octreotide
binding was found in 2 of 5 NFAs, in 1 of 2 prolactinomas, and in the
insulinoma. Two NFAs showed binding of SS28, but not of the sst2.5
specific ligand octreotide. The tumors showed variable sst1 and/or sst3
mRNA expression, whereas no sst2 expression was found. In conclusion, a
dissociation between the inhibitory effects of SS on the one hand and of
the octapeptide SS-analogs octreotide, BIM-23014 and RC-160 on the other
hand, is observed in a small subgroup of NFAs, prolactinomas, and
insulinomas, suggesting that novel sst subtype specific SS-analogs might
be of benefit in the treatment of selected patients with somatostatin
receptor positive secreting tumors not resp
A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients
Treatment with the somatostatin receptor (sst) subtype 2 predominant
analogs octreotide and lanreotide induces clinical and biochemical cure in
approximately 65% of acromegalic patients. GH-secreting pituitary
adenomas, which are not controlled, also express sst(5). We compared the
acute effects of octreotide and SOM230, a new somatostatin analog with
high affinity for sst(1,2,3,5) on hormone release in acromegalic patients.
In a single-dose, proof-of-concept study, 100 microg octreotide and 100
and 250 microg SOM230 were given s.c. to 12 patients with active
acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed
GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%,
respectively; P < 0.01). A comparable suppression of GH levels by
octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7
vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering
effect of 250 microg SOM230 was significantly superior to that of
octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one
patient, the GH-lowering effect of octreotide was better than that of
SOM230. Tolerability for SOM230 was good. Glucose levels were initially
slightly elevated after octreotide and SOM230, compared with control day,
whereas insulin levels were only significantly suppressed by octreotide.
We conclude that SOM230 is an effective GH-lowering drug in acromegalic
patients with the potential to increase the number of patients controlled
during long-term medical treatment