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 endocrine glands of the human foetus are active early in gestation, and various foetal and placental hormonal contributions are essential for growth and sexual differentiation. 1. The anterior pituitary gland has the ability to synthesize, store and secrete hormones early in gestation. The patterns of change in plasma concentrations of hGH (Fig. 1), ACTH, LH and FSH (Fig. 2) during gestation indicate that secretion is at a maximum at mid-gestation, followed by a progressive decrease towards term. The high levels at mid-gestation can be interpreted as due simultaneously to a high secretion rate, low peripheral catabolism and absence of feedback mechanism. In contrast, the secretions of PRL (Fig. 1) and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. 2. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence in the foetal hypothalamus of releasing factors such as LRF (Fig. 5) and TRF, and of somatostatin (Fig. 6), a growth hormone release inhibiting factor (GIF), has been established. TRF and GIF, but not LRF, are also present in the cerebral cortex. It has been postulated that, early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs, and that, later in development, there is a maturation of inhibitory or restraining influences mediated via the CNS (feedback mechanisms) that modulates the secretion of the foetal adenohypophyseal hormones (Fig. 3 and 4). 3. Observations made with anencephalic newborn confirm that a functional hypothalamus is necessary during foetal life for the secretion of each of the hormones of the anterior pituitary gland with the exception of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during foetal life, it appears evident from the anencephaly data that this regulation can only be fully understood by postulating the existence of a growth hormone releasing factor (GRF).
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PMID:[Ontogenesis of hypothalamic control of adenohypophyseal secretions in the human foetus (author's transl)]. 11 47

Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.
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PMID:[Influence of somatastatin on oral glucose tolerance in autonomous hypersecretion of growth hormone, prolactin or insulin (author's transl)]. 17 8

The anterior pituitary gland of the human fetus has the ability of synthetizing, storing and secreting hormones early during gestation. The patterns of plasma concentrations of hGH, ACTH, LH and FSH during gestation indicate a maximum of secretion at mid-gestation followed by a progressive decrease of these concentrations until term. In contrast, the secretions of PRL and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence of releasing factors in the fetal hypothalamus has been established (TRF, LRF, somatostatine) and it was postulated that early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs and, later in development, there was a maturation of inhibitory or restraining influences mediated via the CNS that modulate the secretion of the fetal adenohypophyseal hormones. Observations made with anencephalic newborns confirm that a functional hypothalamus is necessary for the secretions of each of the hormones of the anterior pituitary gland with the exceptiion of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during fetal life, it appears evident that this regulation can only be fully understood with the existence of a GRF (Growth Hormone Releasing Factor).
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PMID:[Hypothalamic factors in the human fetal brain: their role in the ontogeny of fetal hypophyseal functions]. 20 94

Series of studies were performed to elucidate the role of hypothalamic somatostatin in the regulation of growth hormone (GH) release in rats. Somatostatin was determined by a specific radioimmunoassay. In the first series of experiments, the effects of hypophysectomy, thyroidectomy, the administration of hGH and thyroxine on the hypothalamic somatostatin content were examined. Among these treatments, only hypophysectomy resulted in a significant reduction in somatostatin content and none of the rest of treatments altered somatostatin content. These results suggest that somatostatin content in the hypothalamus did rarely change in response to various endocrine treatments when anatomical connections between hypothalamus and pituitary gland were intact. In the second series of experiments, the effects of dopamine, high (K+) and Ca++ on the release of somatostatin from isolated hypothalamic synaptosomes were studied. Dopamine and high (K+) in the media stimulated the release of somatostatin and the latter effect was completely abolished by the removal of Ca++ from the media. The results suggest that dopamine has a role in modulating the release of somatostatin. In the third series, the effects of hypothalamic deafferentation on plasma GH levels and responses to ether stress were examined. Somatostatin content in the hypothalamus was reduced to about 50% in both anterior (AC) and complete deafferented (CC) rats as compared to their respective controls. The mean plasma GH levels were elevated in AC rats and the levels in CC rats were significantly higher than the control. Plasma GH levels 15 min after ether stress reduced significantly in both AC and CC rats, similarly to their respective controls. These findings suggest that the major portion of hypothalamic somatostatin was provided by other regions of the brain, which did not play a role in mediating stress-induced plasma GH reductions, but appeared to be responsible for maintaining basal GH levels.
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PMID:[Role of hypothalamic somatostatin in the regulation of growth hormone secretion in the rat (author's transl)]. 65 86

Plasma immunoreactive growth hormone (hGH) was measured before, during and after the administration of intravenous somatostatin to 3 patients with chronic renal failure and 4 with severe liver disease who had elevation of basal hGH. During somatostatin infusion, the hGH levels declined acutely in a linear fashion when log hGH was plotted against time. Rather surprisingly, the plasma hGH half disappearance time (t 1/2) was 27 min and 18 min in liver and renal disease respectively. These values do not differ from data obtained on normal subjects using exogenous hGH, labelled or unlabelled. Control data on normal subjects using this technique are not available as it was not possible to measure subnormal levels of plasma hGH with the required precision. It is possible that our findings of plasma hGH T 1/2 in liver and renal disease within the normal range reported using exogenous hGH might suggest that high levels of plasma hGH found in these two diseases are primarily caused by hypersecretion rather than impaired clearance.
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PMID:Disappearance rates of plasma growth hormone after intravenous somatostatin in renal and liver disease. 115 52

A three-month study of the effect of growth hormone (hGH) therapy (0.1 U/kg/day sc) on plasma levels of GH releasing hormone (GHRH), somatostatin and insulin-like growth factor I (IGF-I) and on the hGH responsiveness to exogenous GHRH was carried out in 32 prepubertal short-stature children with normal GH secretion. Blood samples were collected prior to initiation of therapy, and at 5, 30 and 90 days of onset of therapy, as well as 2 and 90 days after termination of therapy. The nonconventional hGH therapy induced an increase in serum IGF-I levels which lasted as long as therapy was continued. Plasma GHRH levels showed an early transitory decrease after five days of therapy, whereas plasma somatostatin levels were unaltered. A slight suppression in hGH responsiveness to exogenous GHRH was found at 2 but not at 90 days after termination of hGH therapy. It is concluded that nonconventional hGH treatment does not cause permanent changes in physiological hGH secretion.
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PMID:Growth hormone therapy in normal short children induces a transitory decrease in plasma growth hormone releasing hormone levels and in human growth hormone responsiveness to exogenous growth hormone releasing hormone. 832 Apr 27

Secretion systems engineered for the expression of heterologous protein in E. coli provide several advantages for subsequent isolation of purified product. Proteins released from the periplasmic space, which represent a small fraction (i.e., 4-10%) of total cell protein, can readily be separated from other cellular proteins by centrifugation of the remaining cellular debris or cross-flow ultrafiltration. The starting material derived from secretion systems is generally of higher purity than comparable material produced from strains expressing cytoplasmically for systems exhibiting similar expression levels. The available evidence suggests that recombinant proteins derived from the periplasm are generally, but not always (44-46), soluble in a nonaggregated form. Consequently, simple purification protocols can be effectively employed for producing homogeneous product with a high yield. The majority of the secreted recombinant proteins reviewed in this chapter were purified by simple one- or two-step chromatography procedures. High-resolution techniques such as reversed phase HPLC were found necessary only in cases where the secreted polypeptides were contaminated with proteolytic degradation variants, e.g., hirudin (51) and beta-endorphin (22). The fact that a high level of biological activity has been shown to be characteristic of purified recombinant proteins secreted into the periplasmic space suggests the presence of a native conformation stabilized by the expected disulfide linkages. Intramolecular disulfide bonds most probably form either as the polypeptide is translocated through the cytoplasmic membrane into the periplasm or within the periplasmic compartment, which has a higher oxidation potential than that found in the cytoplasm (57). Studies performed with hGH (31) and muIL-2 (35) provide excellent examples of differences observed in protein folding and disulfide bond formation between heterologous proteins expressed in the cytoplasmic and periplasmic compartments. Thus, hGH and muIL-2 extracted from the cytoplasm of E. coli have been characterized as high molecular weight disulfide-bonded oligomers. It is likely that oligomerization occurs as the polypeptides are released from the reducing environment of the cytoplasm. In contrast, secreted hGH and muIL-2 extracted from the periplasm of E. coli by osmotic shock displayed the properties of a property folded native protein with correct disulfide pairing. In the case of muIL-2 only a small residual fraction (approximately 15%) of the purified secreted protein exhibited incomplete oxidation of cysteine (35). Secretion of heterologous proteins into the periplasm prevents their exposure to the action of proteases located in the cytoplasm of E. coli (58). The smaller polypeptides such as somatostatin (59), IGF-1 (46), and hEGF (54) are known to be particularly susceptible to intracellular degradation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purification of secreted recombinant proteins from Escherichia coli. 136 83

Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics. 182 80

Hypogonadism is a distinct feature of acromegaly, even in the absence of hyperprolactinaemia. In 10 untreated male acromegalics, aged 24 to 46 yr, without evidence of any other disturbance of anterior pituitary function, low testosterone values were found in the presence of a normal reaction of pituitary gonadotrophins following GnRH administration. In three patients, one injection of 5000 IU hCG resulted in a sharp rise in testosterone. Although we were unable to elicit a similar reaction pattern of the GnRH-gonadotrophins-testosterone axis following administration of biosynthetic methionyl-hGH, it is suggested that suppression of testicular function in untreated acromegaly without other endocrine disturbances may be partly caused by increased somatostatin production.
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PMID:Hypogonadism in untreated male normoprolactinaemic acromegalics. 197 48

Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short-stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 +/- 1.05 pmol/l (mean +/- SEM) as compared with 0.51 +/- 0.28 and 0.53 +/- 0.62 during hypoglycemia and exercise (p less than 0.0005 and p less than 0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 +/- 3.2 vs 16.0 +/- 0.8 and 15.3 +/- 1.5 mU/l (p less than 0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin.
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PMID:Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children. 210 91


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