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)

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.
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PMID:Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995. 289 32

We investigated in 6 acromegalic patients the acute effects on glucose tolerance and insulin secretion of a single sc injection of the somatostatin analogue SMS 201-995, performed 4 h before a mixed meal with xylose administration. Growth hormone levels decreased from 34.0 +/- 20.3 (mean +/- SE) to a minimum of 9.3 +/- 3.0 ng/ml, 3 1/2 h after the injection. A significant inhibition of insulin secretion was also noticed, with a fall from 25.3 +/- 6.4 to 6.3 +/- 2.3 microU/ml at 1 h, and a lower and delayed peak level after the mixed meal. However, the postprandial plasma glucose increase was not different from a control day, while plasma xylose levels were lower. Mean glucagon level after SMS 201-995 was lower than control value in 3 out of the 4 patients in whom it was determined. The decrease of serum growth hormone levels, together with partial glucagon inhibition and, more important, a slowing of intestinal absorptive processes, counterbalanced the inhibitory action of SMS 201-995 on insulin secretion, and no deterioration in carbohydrate tolerance could be demonstrated. However, before SMS 201-995 is employed in the management of acromegalic patients refractory to surgery and bromocriptine therapy, we need further observations of postprandial glycemic profiles during long-term therapy with multiple daily injections of the compound.
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PMID:Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal response to a mixed meal in acromegalic patients. 289 7

Growth hormone releasing factor (GHRF) was examined to determine whether it affects somatostatin (SRIF) release from cultured rat hypothalamic cells and fragments in vitro. The hypothalami of rat fetuses were collected on the 17th day of pregnancy under a dissection microscope. Thirty hypothalami were placed in phosphate buffered saline, and the cells were dispersed with 0.1% collagenase. The dispersed cells were cultured in Dulbecco's modified Eagle medium (DMEM) containing 10% horse serum and 2.5% fetal calf serum at 37 degrees C under 5% CO2 in air. On the 12th day of culture, the cells were washed with Krebs Ringer bicarbonate buffer containing glucose (KRBG), and then incubated with KRBG for 1 hour. The medium was replaced with KRBG alone (control) or KRBG containing test substances, and incubated for another hour. SRIF released into the medium was quantitated by RIA. The mean basal release of SRIF was 14.7 +/- 0.9 pg/dish/hour. One-tenth, 1, and 10nM hpGRF44 stimulated SRIF release by 1.4, 1.5, and 1.8 fold respectively in a dose-related manner. Ten nM ovine corticotropin releasing factor (o-CRF) also stimulated SRIF release by 2.3 fold. One, 10, and 100 nM hpGRF44, 10nM o-CRF, 10nM thyrotropin releasing hormone (TRH) and 60 mM K+ also stimulated SRIF release from rat hypothalamic fragments. Removal of Ca++ from the medium resulted in a decrease of basal release of SRIF. In Ca++ free medium, 10nM hpGRF44 failed to release SRIF. One-tenth nM hpGRF44, 10nM GnRH, and 10nM VIP have no effect on SRIF release statistically. The results of this study demonstrate that a high concentration of GHRF stimulates SRIF release from the hypothalamus in vitro, suggesting a possibility that GHRF may increase the release of SRIF from the median eminence and the hypothalamus in vivo under certain conditions.
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PMID:The stimulation of somatostatin release by hpGRF44 from rat hypothalamic cells and fragments in vitro. 289 40

Growth hormone (GH) production of the anterior pituitary gland is controlled by inhibiting and releasing hormones that are synthesized in the diencephalon. In order to elucidate the possible interrelationships between somatostatin and growth hormone-releasing factor (GRF) synthesizing neurons at the hypothalamic level, immunocytochemical double labelling studies were performed on sections containing the arcuate nucleus (ARC) of the rat. Somatostatin producing neurons were located in the dorsomedial part of the ARC, while somatostatin immunoreactive (IR) axons were found in the ventro-lateral part of the nucleus, an area containing GRF-synthesizing cells. The use of the dual antigen localization technique revealed the approach and juxtaposition of somatostatin containing axons to dendrites and cell bodies of GRF-synthesizing neurons. At the light microscopic level, several somatostatinergic axon varicosities were clustered around single GRF-synthesizing cells. Ultrastructural analysis of the ventro-lateral part of the ARC showed that (i), somatostatinergic axons established synaptic connections (ii), GRF-producing neurons received axons terminals on their somata and dendrites and (iii), somatostatin-IR axons formed asymmetric synaptic specializations with both dendrites and somata of GRF-synthesizing neurons. These morphological findings indicate that the hormone production and release of hypophysiotrophic GRF-IR neurons can be influenced by the central somatostatin system via direct synaptic mechanisms. The data support the concept, that the interaction of inhibiting and releasing hormones, which determines responses of the pituitary target cells, may take place also at the hypothalamic level.
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PMID:Synaptic communication between somatostatinergic axons and growth hormone-releasing factor (GRF) synthesizing neurons in the arcuate nucleus of the rat. 290 Feb 29

Growth hormone (GH) secretion by the somatotrope is under dual regulation by the hypothalamic peptides, somatostatin (SS) and GH-releasing hormone (GHRH). Cytosolic free calcium concentration and cumulative GH release were measured simultaneously in anterior pituitary cells from adult male rats. This was made possible using a combination of digital imaging video microscopy with the fluorescent calcium indicator Fura-2 and the reverse haemolytic plaque assay (RHPA) to identify the cell type and measure hormone secretion from the cells under study. This technique allows calcium measurements to be made at very short time intervals (less than 150 ms) in single cells. Spontaneous calcium transients were demonstrated in 85% of GH plaque-forming cells. These occurred at a frequency of 2-13 min-1 and had an amplitude of 50-500 nmoll-1. The somatotropes with the largest calcium fluctuations produced the largest plaques; thus, the calcium transients appeared to correlate with hormone release. Since the somatotrope alone shows these fluctuations, the mean intracellular calcium concentration is 238 +/- 18 nmoll-1 in somatotropes and 113 +/- 8 nmoll-1 in non-somatotropes. Upon exposure to SS (1 nmoll-1) intracellular calcium fell from 200-250 nmoll-1 to 50-100 nmoll-1 with an apparent reduction in oscillations. Withdrawal of SS increased the intracellular calcium level. GHRH increased intracellular calcium but 10 nmoll-1 GHRH given simultaneously with 1 nmoll-1 SS reduced intracellular calcium to that level observed during SS alone. Thus, the SS effect on intracellular calcium predominates. The effects of SS can be mimicked by removal of extracellular calcium, or by the addition of CoCl2 (2 nmoll-1) or by verapamil (100 mumoll-1), two agents which block calcium channels. The hormone secretion index (indicated by the area of the plaque formed in RHPA) enables us to demonstrate that GHRH in this system increases GH secretion, and SS inhibits it. In combination, GHRH and SS oppose one another. Spontaneous calcium oscillations are characteristic for normal somatotropes. These oscillations are related to spontaneous hormone secretion and due to influx of calcium through ion channels in the membrane. Intracellular signalling information may be encoded in both frequency and amplitude of calcium oscillations. The actions of GHRH and SS on regulation of GH secretion are proposed to be mediated, at least in part, by regulation of intracellular cytosolic free calcium. This modulation is dependent on extracellular calcium concentrations. We are now investigating the molecular mechanisms involved in this process.
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PMID:The somatotrope: an endocrine cell with functional calcium transients. 290 79

Growth hormone (GH) pulses in vivo are associated with increased hypothalamic portal growth hormone releasing hormone (GH-RH) concentration and can be prevented by GH-RH antisera. GH pulses are also associated with prior reduction of portal somatostatin (SRIF) concentrations, although SRIF antisera do not abolish GH pulses. In vitro, pulses of GH-RH as well as SRIF withdrawal are followed by pulses of GH release; the presence of GH-RH enhances post-SRIF GH release. We asked four questions: (1) During combined GHRH-SRIF exposure in vitro, must SRIF withdrawal be complete to produce a pulse of GH release, or is there a threshold diminution of SRIF which permits it? (2) When pulsatile GH release does occur, is it an all-or-none phenomenon, or is it titratable by fractional reduction of SRIF? (3) Does varying the GH-RH concentration while administering SRIF systematically alter GH release in response to fractional SRIF reduction? (4) Given a small but distinct effect of GH-RH on release of stored prolactin (PRL) in this system, does fractional SRIF reduction alter PRL release in parallel? Rat pituitary tissue whose hormone stores had been prelabeled with tritium was perifused for 120 min in combined 25 nM SRIF and 3 or 10 nM rat GH-RH (rGH-RH). Then, while maintaining rGH-RH concentrations, the SRIF concentration was left unchanged (control) or was reduced to 20, 15, 10, 5, or 0 nM for 60 min. Release of stored rGH and rPRL was assessed by immunoprecipitation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fractional reduction of somatostatin concentration interacted with rat growth hormone releasing hormone to titrate the magnitude of pulsatile growth hormone and prolactin release in perifusion. 290 14

In this report, we described the clinical, radiographic, and echocardiographic findings in a cat with hypersomatotropism and insulin-resistant diabetes mellitus. Growth hormone determinations were made because of persistent hyperglycemia despite insulin requirements exceeding 2.2 U/kg of body weight, and the acromegalic features of the cat. Also, the results of a therapeutic trial in which a long-acting analogue of somatostatin was used are discussed.
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PMID:Hypersomatotropism and insulin-resistant diabetes mellitus in a cat. 291 4

Growth hormone releasing factors (GRFs) have been isolated from human pancreatic tumours (hGRF) and rat hypothalamus (rhGRF). The response to GRF at the pituitary level can be modulated by other factors, including glucocorticoids, thyroid hormones, somatostatin and other neuropeptides and somatomedins. Glucocorticoids enhance GRF-induced growth hormone (GH) secretion in primary cultures of rat anterior pituitary cells, and the synthetic glucocorticoid dexamethasone has recently been shown to increase the amounts of GH released in freely moving rats in response to submaximal doses of intravenous GRF. To investigate whether somatotroph sensitivity to GRF is modulated at its receptor level, we have developed a radioreceptor assay using an iodinated analogue of hGRF as radioligand. We report here that the relative binding affinities of rGRF, hGRF and the two analogues are correlated with their in vitro biological potencies. Further, the number of GRF binding sites is drastically decreased in cells deprived of glucocorticoids either in vivo or in vitro.
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PMID:Binding sites for growth hormone releasing factor on rat anterior pituitary cells. 298 7

Growth hormone pulse amplitude is intimately connected with growth in childhood. Its effects are most clear in middle childhood, although the influence of adrenal androgens is probably also important. In infancy, nutrition plays an important part and, in the adolescent growth spurt, the synergism with sex steroids is important. Detailed attention needs now to be focussed on the mechanisms by which growth hormone is secreted and has its action; these include the effects of GHRH, somatostatin, insulin and IGF-I.
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PMID:Growth and growth hormone secretion. 305 53

Growth and lactation are complex processes controlled by several metabolic hormones such as insulin, glucagon, and thyroid hormones but most notably growth hormone. Growth hormone secretion is regulated by two hypothalamic hormones, somatostatin, an inhibitory regulatory factor, and growth hormone-releasing factor. The quantity and pattern of growth hormone secretion is ultimately regulated in concert by the secretion of both regulatory factors from the hypothalamus through the hypothalamo-hypophyseal portal system, where they exert their actions at unique pituitary receptors. Because the potential use of exogenous growth hormone administration for the stimulation of growth efficiency and lactation has been demonstrated, recent efforts have been directed toward the enhancement of production through manipulation of endogenous growth hormone secretion via its releasing factor. Thus far, releasing factor-stimulated growth and lactation has not been achieved to the same extent as that of exogenous growth hormone. Growth hormone-releasing factor has stimulated growth in two growth hormone-deficient children, as well as female, but not male, rats. Although all food-producing species tested to date respond to growth hormone-releasing factor with the appropriate growth hormone response, continuous or pulsatile administration of releasing factor has not resulted in increased growth rate in sheep, chicks, or hogs. Despite levels of circulating growth hormone that would be expected to produce a 30% increase in milk production if given exogenously to dairy cows, releasing factor-stimulated growth hormone secretion has resulted in only a 3 to 9% increase. It is clear from these studies that further developments are necessary to demonstrate the practical application of growth hormone-releasing factor.
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PMID:Growth hormone-releasing factor effects on pituitary function, growth, and lactation. 310 44


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