Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten acromegalic patients were treated with the somatostatin analogue SMS 201-995 (SMS) for 3-38 weeks in various doses and by different administration routines (thrice daily or multiple sc injection). Plasma GH daily profiles, plasma IGF-I, urinary GH, serum TSH, IRI and fasting blood glucose (FBG) concentrations were measured before and during SMS treatment. Plasma GH rapidly decreased within one hour in all patients and was suppressed for at least 4 h after a 50 micrograms sc injection of SMS in 8 patients. Multiple injections of 300-600 micrograms/day SMS (25-50 micrograms X 12) suppressed GH throughout the day. Plasma IGF-I was completely normalized in 4 patients, and, in all but one of the others, decreased markedly. Urinary GH decreased within the first week of treatment in all patients and normalization was obtained in 3 patients. Shrinkage of the pituitary tumor, as determined by CT or MRI, was observed in 7 of 9 patients. Other clinical improvements, such as diminution or complete disappearance of swelling of soft tissues, excessive perspiration, and headache, were observed in 7 of 8 patients. Changes in serum TSH, IRI and FBG were seen in 3-4 patients, but without any apparent clinical problems. In conclusion, SMS is a useful clinical tool for treatment of acromegaly, and a multiple sc injection method seems to be preferable.
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PMID:Treatment of acromegaly with long acting somatostatin analogue SMS 201-995. 322 51

GH secretion is stimulated by hypothalamic GH-releasing factor (GHRH) and inhibited by somatostatin. Since GH induces the production of insulin-like growth factors (IGF) in liver and other tissues, it is of interest to learn whether IGF alters GH release through long loop feedback inhibition. Pituitary adenomas which had been removed from six acromegalic patients were processed for dispersed cell cultures and/or cell membrane preparations. Binding studies using 125I-labeled IGF-I, IGF-II, and insulin revealed specific hormone binding for each ligand to cell membranes derived from four somatotropinomas. A partially purified somatomedin preparation inhibited basal and/or GHRH-stimulated GH release from cultured pituitary cells derived from three of four adenomas; there was no effect of somatomedin in one tumor. In a single tumor, insulin also partially inhibited GHRH-stimulated GH release. Additionally, in one nonadenomatous pituitary removed from a patient with diabetes mellitus, insulin and somatomedin inhibited GHRH-stimulated GH release, and insulin inhibited basal GH secretion. These results indicate that specific cell membrane receptors for somatomedin peptides and insulin may be found on cell membranes from GH-secreting tumors, and that somatomedins and insulin can inhibit GH release in cultured human somatotropinoma cells. Thus, these data suggest that somatomedins may exert feedback inhibition of GH secretion in some patients with acromegaly.
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PMID:Regulation of growth hormone release from cultured human pituitary adenomas by somatomedins and insulin. 388 29

IGF-I acts as a renotropic factor in early streptozotocin-induced diabetes. Somatostatin analogue (octreotide) treatment initiated at the onset of diabetes prevents kidney IGF-I accumulation and renal growth. Seven days of octreotide treatment initiated after 3, 5, 7 or 9 days of untreated diabetes was investigated. Diabetic renal hypertrophy was followed by renal hyperplasia. Compared with placebo-treated diabetic rats, the earliest octreotide intervention was followed by a greater reduction in renal growth compared with intervention later on (days 3 to 10, 12%; days 5 to 12, 10%; days 7 to 14, 9%; days 9 to 16, 6%; P < 0.05). Octreotide treatment was unable to reduce protein accumulation and kidney DNA increase consistently. No difference in glomerular volume fraction or total glomerular volume was observed between placebo- and octreotide-treated diabetic rats. Octreotide treatment was followed by reduced kidney and serum IGF-I especially following early intervention, while no effect over that of diabetes was observed in the later intervention periods. The results confirm the notion that initial renal IGF-I accumulation is a prerequisite for early diabetic kidney hypertrophy in rats and show that delayed octreotide treatment cannot reverse renal and glomerular growth which is already manifest.
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PMID:Effect of octreotide on experimental diabetic renal and glomerular growth: importance of early intervention. 749 May 42

It was demonstrated recently that administration of lanreotide and octreotide, two somatostatin octapeptide analogs, increased circulating insulin-like growth factor binding protein 1 (IGFBP-1) levels. The present study demonstrates that native somatostatin 14 shares this ability and that the increase in abolished by concomitant hyperinsulinemia within the physiological range. Five fasting healthy volunteers underwent a hyperinsulinemic as well as a normo-insulinemic (i.e. basal insulinemic) euglycemic clamp lasting 8 h (serum insulin levels remained constant, about 570 vs. 16 pmol/L). Immediately before the clamps, a somatostatin infusion (500 micrograms/h) was started and continued throughout. During normo-insulinemia, IGFBP-1 levels increased slowly from 6.3 +/- 6.2 to 36.1 +/- 14.8 micrograms/L (P < 0.05) reaching maximum after 7 h constant somatostatin infusion, whereas hyperinsulinemia induced a significant decrease from basal levels (from 4.7 +/- 5.4 to 1.1 +/- 1.5 micrograms/L) after 8 h (mean +/- SD, n = 5). These results may indicate hitherto unnoticed interactions of somatostatin and insulin on IGFBP-1 release with possible impact on IGF-I action at the cellular level.
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PMID:Somatostatin-stimulated insulin-like growth factor binding protein-1 release is abolished by hyperinsulinemia. 750 19

The effects of a chronic treatment with octreotide were evaluated in 19 patients affected with functionless pituitary adenomas. Octreotide caused a significant decrease of GH and IGF-I levels in all the patients and no significant change in thyroid, adrenal and gonadal function. In contrast, during the therapy, the glucose response to an oral glucose tolerance test considerably increased and was delayed, while the insulin response decreased and was delayed. Serum alpha-subunit (alpha-SU) was above normal in 10 of 16 patients in which this evaluation was performed: octreotide caused a significant decrease (p < 0.01) of alpha-SU levels in 6 of these 10 patients. Octreotide did not induce any significant change in visual fields except in 1 patient, who had a great improvement of visual perimetry and a decrease of alpha-SU levels but unmodified CT scan features. In our series of patients, octreotide was ineffective in reducing tumor mass. The efficacy of octreotide might rely on the presence of somatostatin receptors on adenoma-cell membranes. Therefore patients with functionless adenomas to be treated with octreotide might be identified with pituitary scintiscan using the recently available labeled 111In-octreotide.
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PMID:Effects of a chronic treatment with octreotide in patients with functionless pituitary adenomas. 750 80

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 +/- 4.4 to 149.3 +/- 22.2 muU/l (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-I concentration increased from 0.67 +/- 0.04 to 0.99 +/- 0.10 micrograms/l (p = 0.005) and the IGFBP-3 concentration rose from 13.4 +/- 1.25 to 17.5 +/- 1.83 micrograms/l (p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 +/- 36.0 to 234.3 +/- 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 +/- 0.6 to 3.7 +/- 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive beta-endorphin increased from 24.4 +/- 1.8 to 29.9 +/- 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, somatostatin or corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. 753 55

Beta adrenergic receptors mediate the inhibitory influence of catecholamines on GH secretion in man, likely via stimulation of hypothalamic somatostatin release. To further clarify the role of beta adrenergic receptors in the neural control of GH secretion, in 7 normal females (age 21-27 yr) we studied the interaction of salbutamol (SAL 0.08 mg/kg orally), a beta 2-adrenergic agonist, with GHRH (1 microgram/kg i.v.) and/or galanin (GAL 15 micrograms/kg i.v.), a neuropeptide endowed with a GH-releasing effect which is likely mediated by concomitant stimulation of GHRH- and inhibition of somatostatin-secreting neurons. SAL inhibited the GH response to GHRH (AUC: 282.6 +/- 102.7 vs 1083.6 +/- 176.5 micrograms/l/h, p < 0.05) and, although not significantly, that to GAL (263.9 +/- 103.7 vs 418.4 +/- 70.4 micrograms/l/h). GAL enhanced the GHRH-induced GH rise (2129.5 +/- 362.2 micrograms/l/h, p < 0.05) but SAL pretreatment inhibited this effect (1249.8 +/- 257.1 micrograms/l/h, p < 0.02) so that the GH response to the combined administration of GHRH, GAL and SAL overlapped with that to the neurohormone alone. In conclusion, our results show that the inhibitory influence of beta adrenergic activation on GH secretion overrides the stimulatory one of galanin. They strengthen the view that in man beta-adrenergic receptors and galanin modulate GH secretion having opposite influences aimed to balance the function of the GH-IGF-I axis.
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PMID:Interaction of salbutamol and galanin on both basal and growth hormone releasing hormone-stimulated growth hormone secretion in humans. 759 18

In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.
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PMID:Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat. 761 36

Transgenic mice expressing a tyrosine hydroxylase-human (h) GH fusion gene in the hypothalamus exhibit a dwarf phenotype. The GH feedback mechanism(s) underlying the growth retardation in these animals was investigated by assessing peptide and messenger RNA (mRNA) levels of the hormones of the hypothalamic-GH-IGF-I axis. Pituitary GH content, hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) content, and serum IGF-I levels were measured by RIA. mRNA levels of hypothalamic GHRH and SRIH and of pituitary GH and the GHRH receptor were measured by Northern blot hybridization. Transgenic mice of both sexes and their wild-type littermates were studied at 2-4 months of age. The pituitary GH content was markedly reduced by 85% in male and by 87% in female transgenic mice compared to that in wild-type controls (P < 0.01 for both). The pituitary GH mRNA content was also decreased by 73% (P = 0.002) in transgenic male mice. Circulating IGF-I levels were significantly reduced by 66% and 68% in male and female transgenic mice, respectively (P = 0.001). The hypothalamic GHRH content was significantly reduced by 19% and 33% (P < 0.05) in male and female transgenic mice, respectively. No significant difference was detected, however, in the hypothalamic SRIH content between wild-type and transgenic mice. Hypothalamic GHRH mRNA levels were significantly decreased by 35% (P = 0.002) in transgenic male mice compared to those in wild-type littermates. In contrast, SRIH mRNA was not significantly changed. An even greater reduction (61%; P = 0.003) was observed in pituitary GHRH receptor mRNA in transgenic mice. These data indicate that the GH deficiency and dwarf phenotype of the tyrosine hydroxylase-hGH transgenic mouse can be attributed primarily to impaired hypothalamic GHRH production. The mechanism of GH feedback inhibition appears to involve direct suppression of GHRH gene expression by locally produced hGH in the hypothalamus.
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PMID:Autofeedback suppression of growth hormone (GH) secretion in transgenic mice expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking sequences to the hypothalamus. 764 13


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