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)

The in vivo incorporation of [35S]cysteine into hypothalamic somatostatin-28 was found to be substantially below normal in hypophysectomized rats. A smaller reduction in label incorporation into arginine vasopressin was also observed, while incorporation into acid-precipitable protein was normal. The diminution in somatostatin biosynthesis presumably reflects the absence of pituitary growth hormone secretion, while that in vasopressin synthesis may reflect the loss or disruption of vasopressin-producing cells.
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PMID:Effect of hypophysectomy on somatostatin-14 and somatostatin-28 biosynthesis in the rat hypothalamus. 287 92

Twelve patients with active acromegaly, six of whom had not responded to previous combined surgery, radiotherapy, and bromocriptine administration, were treated with an octapeptide long-acting somatostatin analogue, SMS 201-995, given subcutaneously for up to 1 year. Growth hormone (GH) levels decreased by 50% to 90% after a single 25-micrograms SMS 201-995 injection in all patients, including two who were resistant to bromocriptine therapy. After GH values reached a nadir, they returned to preinjection values over a 12-hour period and no rebound was seen. Assessment of the GH-lowering effect of the drug at weekly intervals for the first 6 weeks and monthly thereafter disclosed no tachyphylaxis. Gradual increase of the dose from 50 to 150 micrograms daily led to a significant increase in clinical improvement. Shrinkage of the size of the pituitary tumor was documented in three of nine evaluated cases. Abdominal cramps of a transient nature not associated with diarrhea were noted in two patients but there were no other side effects. Hematological and biochemical blood and urine tests, including serum thyroxine and cortisol levels, did not reveal any abnormality during chronic treatment. This study demonstrates the safety and efficacy of SMS 201-995 in the short-term treatment of acromegaly.
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PMID:Therapeutic efficacy of a somatostatin analogue (SMS 201-995) in active acromegaly. 287 84

Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels.
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PMID:Huntington's disease: effect of cysteamine, a somatostatin-depleting agent. 287 27

Growth hormone (GH) is important in diabetes in view of its anti-insulin actions and its relation to the long-term complications of the disease. The suppression of GH secretion in diabetics has theoretical and possible therapeutic interest. Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones. It also has inhibitory effects on gastrointestinal motility, exocrine secretion, nutrient absorption, and splanchnic blood flow. Its therapeutic use is limited by a duration of effect of several minutes only. SMS 201-995 holds more potential than native somatostatin in view of its longer duration of action. Preliminary data suggest that 50 micrograms SMS 201-995 subcutaneously at night inhibits the nocturnal rise in GH secretion in normal man, but no effect on 24-h GH secretion is observed when SMS 201-995 is injected twice daily before meals. SMS 201-995 inhibits secretion of insulin, glucagon, and TSH in addition to growth hormone and induces carbohydrate intolerance when administered before food in normal subjects. Gastrointestinal side effects suggest additional effects on nutrient disposal, which are important when it is administered before food. Further studies are required to elucidate these effects of SMS 201-995 on endocrine and gastro-intestinal function in normal and diabetic man.
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PMID:Effects of somatostatin and SMS 201-995 on carbohydrate metabolism in normal man. 287 1

The brain peptide human growth hormone releasing factor (1-40) (GRF), which stimulates adenylate cyclase activity in the anterior pituitary, is the predominant hormone signal for pituitary growth hormone (GH) release. Activators of protein kinase C such as teleocidin and 4 beta-phorbol 12-myristate 13-acetate (PMA) double the cyclic AMP accumulation induced by GRF, with no apparent effect on GRF potency; an inactive 4-alpha-PMA has no such action in cultured anterior pituitary cells. This PMA potentiation can be measured as early as 60 s, is maximal by 15 min, and wanes such that by 3-4 h there is no such amplifying effect of PMA. PMA, phorbol 12,13-dibutyrate, and teleocidin ED50 values for potentiating GRF activity are similar to those obtained for direct protein kinase C activation. The major inhibitory peptide somatostatin reduced both GRF- and GRF + PMA-stimulated cyclic AMP accumulation. Pertussis toxin totally blocked this somatostatin action without affecting the degree of maximal GRF potentiation achieved with PMA. Thus, the pertussis toxin target(s) are required for somatostatin inhibition of the cyclic AMP generating system, but may not be involved in the PMA potentiation of GRF-stimulated cyclic AMP accumulation.
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PMID:Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin. 287 83

Growth hormone, prolactin and somatostatin-like immunoreactivities were demonstrated in the brains of larval, young adult (parasitic) and upstream migrant adult sea lampreys, Petromyzon marinus, by means of immunoperoxidase techniques. Growth hormone (GH) and prolactin (PRL) were observed within separate perikarya in the nucleus praeopticus, within fibers in the commissura praeinfundibularis, and in nerve endings within the neurohypophysis of larval and adult-stage lampreys. Cell bodies demonstrating immunoreactive growth hormone were more numerous than those reactive for prolactin. Unlike in the upstream migrant adult lamprey, no GH or PRL was demonstrated in the adenohypophysis of larval or parasitic lamprey. Somatostatin (SRIF)-like immunoreactive neurons were demonstrated in the nucleus commissurae praeinfundibularis, anterior and posterior pars ventralis hypothalami, pars dorsalis thalami, and the tegmentum motorium rhombencephali of larval, parasitic and upstream migrant adult lampreys. Many of the SRIF containing neurons within the hypothalamus were cerebrospinal fluid (CSF)-contacting cells. SRIF fibers were found throughout most of the brain predominating within the nucleus praeopticus, pars ventralis hypothalami, and the nucleus interpeduncularis. No SRIF immunoreactivity was found within the neurophyophysis. The possible functions of these peptides within the brain of the lamprey are discussed.
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PMID:Immunocytochemical demonstration of growth hormone, prolactin and somatostatin-like immunoreactivities in the brain of larval, young adult and upstream migrant adult sea lamprey, Petromyzon marinus. 287 40

Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-I (27 nM) only reduced the GRF-stimulated growth hormone release by 27 +/- 3% (N = 5). Cycloheximide (15 micrograms/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools.
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PMID:Cycloheximide blocks insulin-like growth factor I but not somatostatin inhibition of growth hormone secretion. 288 2

The use of biotechnology now allows adequate supplies of previously scarce substances. This has enabled evaluation of some of these substances as enhancers of animal performance. Growth hormone (GH) shows promise as a stimulator of lactation in a number of species, but its effects on the stimulation of growth are somewhat equivocal. Somatocrinin, by virtue of its GH- releasing activity, may also be potentially useful, though to date the effects of somatocrinin administration have been less promising than those for GH directly. Somatomedin (IGF-1), as the active mediator of GH, might be expected to be useful in growth promotion but, as yet, it has not been convincingly demonstrated to stimulate growth in normal animals. All these hormones have the major drawback that, until a suitable slow-release/delivery mechanism is available, they need to be administered very frequently. An alternative approach, immuno-neutralization of the growth inhibiting effects of somatostatin, has been demonstrated to enhance growth; although at present still requiring multiple treatments such a technique potentially has many advantages.
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PMID:Biotechnology in the potential practical application of somatotrophic hormones for improving animal performance. 288 69

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.
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PMID:The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones. 288 54

Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal.
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PMID:Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro. 289 1


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