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)

Cytosolic free calcium ions concentration ([Ca2+]i) was measured in cell suspensions of cultured human IM-9 lymphocytes by dual wavelength fluorescence spectrometry using the calcium probe fura-2. Human GH (0.2-50 nM) induced a slow, progressive and sustained increase in [Ca2+]i. The GH effect was specific and exhibited a biphasic pattern, presumably reflecting GH receptor dimerization, typical of some other GH actions. The hGH effect depended on extracellular calcium, suggesting that at least part of the [Ca2+]i increase was due to a stimulation of calcium influx. GH did not increase IP3. Somatostatin-14 in the range 10(-10) to 10(-8) M, while having no effect of its own on [Ca2+]i, inhibited the effect of hGH. This inhibition by somatostatin was prevented by pretreatment of the cells with pertussis toxin. The hGH-induced [Ca2+]i increase was not related to either protein tyrosine phosphorylation or protein kinase C activation, thus suggesting a novel mechanism of GH transmembrane signalling.
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PMID:Human growth hormone increases cytosolic free calcium in cultured human IM-9 lymphocytes: a novel mechanism of growth hormone transmembrane signalling. 803 38

The half-lives of endogenous and exogenous (biosynthetic monomeric) GH were compared in the morning and evening in healthy young men (n = 10). In group A, a bolus of GHRH was injected either at 0800 or at 2000 h, whereas in group B hGH was injected iv after suppression of endogenous GH by somatostatin. GH was sampled every 10 min and the t1/2 for GH was determined by deconvolution analysis (two compartments). The GH elimination half-life was shorter in the morning: for endogenous GH, t1/2 was 23 +/- 1.1 min (mean +/- SE) in the morning compared to 26 +/- 1.7 min in the evening (P < 0.02). T1/2 correlated negatively with estradiol (r = -0.78; P < 0.01) and positively with sex hormone-binding globulin (r = 0.71; P < 0.03). The half-life of exogenous 22-kilodalton GH was shorter compared to endogenous GH (P < 0.002), and diurnal variation was even more pronounced: t1/2 was 14 +/- 1.0 min in the morning and 19 +/- 1.0 min in the evening (P < 0.01). These effects were not due to differences in GH distribution volumes. The half-life of exogenous GH was significantly affected by weight (r = -0.8; P < 0.01) and height (r = 0.67; P < 0.05). We conclude that in young males, the rate of GH disappearance from the circulation depends on both diurnal mechanisms as well as the source or structural composition of the hormone. Body size and sex steroids contribute to the variability of GH clearance in healthy man.
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PMID:Diurnal variation in the elimination rate of human growth hormone (GH): the half-life of serum GH is prolonged in the evening, and affected by the source of the hormone, as well as by body size and serum estradiol. 832 45

Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli; in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opiods induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline; (b) a met-enkephalin analog G-DAMME 250 micrograms IV as a bolus at time 0'; (c) hGH 2 IU as an IV bolus at time -180'; (d) G-DAMME as above, preceded by hGH as above. In our study, G-DAMME stimulated GH secretion both basally (peak 17.9 +/- 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 +/- 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded.
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PMID:Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. 859 Sep 60

Dwarf tyrosine hydroxylase-human GH (TH-hGH) transgenic mice carrying the hGH reporter gene targeted by the TH promoter express hGH in those regions of the hypothalamus responsible for regulation of pituitary GH secretion. Central expression of the hGH gene decreases GH-releasing hormone (GHRH) and increases somatostatin, which ultimately impacts on pituitary function by reducing the overall amount of GH produced. In the present study, we sought to determine if the reduction of pituitary GH in TH-hGH mice could be attributed to a decrease in somatotrope cell numbers and/or an impairment of somatotrope function. Pituitaries from TH-hGH or wild-type (WT) male and female mice were enzymatically dispersed, counted, and immunostained for GH, PRL, TSH, and ACTH. The total number of pituitary cells recovered from TH-hGH pituitaries was approximately one-half of that from WT controls. However, the proportion of cells that stained for GH and PRL were virtually identical (males, GH-TH-hGH, 58.1 +/- 1.0% [mean +/- SEM] vs. WT, 60.7 +/- 1.0%; PRL-TH-hGH, 43.4 +/- 2.2% vs. WT, 43.1 +/- 0.7%; females, GH-TH-hGH, 47.9 +/- 2.3% vs. WT, 41.5 +/- 3.5%; PRL-TH-hGH, 43.3 +/- 3.2% vs. WT, 47.1 +/- 3.3%). In contrast, percentages of both TSH- and ACTH-containing cells were increased in TH-hGH pituitaries relative to controls (males, TSH-TH-hGH, 15.1 +/- 2.3% vs. WT, 9.6 +/- 1.5%; ACTH-TH-hGH, 24.5 +/- 2.5% vs. WT, 10.9 +/- 0.9%; females: TSH-TH-hGH, 11.3 +/- 0.7% vs. WT, 7.5 +/- 0.6%; ACTH-TH-hGH, 19.8 +/- 1.6% vs. WT, 9.3 +/- 0.8%; P < 0.05). Calculation of the absolute number of each cell type per pituitary demonstrated TH-hGH mice to have about one-half the number of GH and PRL cells, whereas TSH and ACTH cell populations were comparable with that of their WT counterparts. Immunocytochemical localization of GH cells within pituitary sections from TH-hGH mice revealed that somatotropes were confined primarily to the lateral wings of the adenohypophysis, in contrast to the heterogeneous distribution of GH-immunostained cells in WT pituitaries. To assess the functional capacity of the somatotrope populations, pituitary cells from TH-hGH and WT mice were challenged with mouse GHRH (0.01-10 nM). The quantity of GH released (as assessed by both RIA and reverse hemolytic plaque assay) under basal and stimulated conditions did not differ among TH-hGH and WT pituitary cell cultures. Similarly, GHRH induced intracellular cAMP levels were comparable. These results indicate that proliferation of pituitary somatotropes and lactotropes is much more sensitive to changes in GHRH input than is the capability of developing regulated GH secretory function.
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PMID:The tyrosine hydroxylase-human growth hormone (GH) transgenic mouse as a model of hypothalamic GH deficiency: growth retardation is the result of a selective reduction in somatotrope numbers despite normal somatotrope function. 889 26

Mice transgenic for heterologous and ectopic GH expression serve as models for studying the feedback effects of elevated nonregulated GH on hypothalamic hypophysiotropic neurons as well as on peripheral function. For example, hypothalamic somatostatin expression has been shown to be increased markedly in mice bearing either bovine (b) or human (h) GH transgenes. Human, but not bovine, GH has lactogenic properties in mice, and appears to stimulate PRL-inhibiting tuberoinfundibular dopaminergic (TIDA) neurons. The present study was designed to determine the effect of a lifelong excess of hGH on dopamine (DA) expression in and numbers of TIDA neurons. Male mice of four transgenic lines were examined. The transgenic animals bore constructs of either bGH or hGH fused to either metallothionein (MT) or phosphoenolpyruvate carboxykinase (PEPCK) promoters; brains of transgenic mice were compared morphologically with those of nontransgenic littermates. Formaldehyde-induced catecholamine histofluorescence and tyrosine hydroxylase (TH) immunocytochemistry were examined in alternate brain sections; cell number was quantified for TIDA neurons (area A12) and a nonhypophysiotropic diencephalic DA area, the medial zona incerta (A13). Body weights were higher (P < 0.01) in PEPCK-GH than in MT-GH transgenic mice, as were serum levels of heterologous GH in those lines. In MT-hGH, but not MT-bGH or PEPCK-bGH, transgenic mice, A12 perikaryal fluorescence was enhanced, and ME fluorescence was reduced compared with those in control animals. The reduced ME DA is likely to reflect stimulation of TIDA neurons, because A12 TH-immunoreactive neuron number was increased by 34% in MT-hGH mice compared with that in controls (P < 0.05). In mice bearing the PEPCK-hGH construct, A12 TH neuron number was increased 47% (P < 0.001) compared with that in littermate controls. There were no differences in A13 cell number among animals, and A12 cell numbers in mice expressing bGH did not differ from control values. These results suggest that although extremely high levels of circulating bGH do not stimulate TIDA neurons, lifelong high levels of hGH have a stimulatory and graded effect on developmental differentiation of these cells for TH and DA production, supporting the concept of PRL as a trophic factor for TIDA neurons.
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PMID:Stimulatory effect of human, but not bovine, growth hormone expression on numbers of tuberoinfundibular dopaminergic neurons in transgenic mice. 920 27

Autoregulation of GH secretion in sheep was examined by intravenous and intracerebroventricular (i.c.v.) administration of human and bovine GH. Intravenous administration of hGH at either 2 mg or 10 mg per sheep failed to alter radioimmunoassayable plasma ovine GH concentrations or plasma somatostatin. Human GH also failed to alter plasma oGH when given at a dose of 50 micrograms i.c.v. Bovine GH (at 50 micrograms or 500 micrograms) i.c.v. did not affect basal plasma oGH or somatostatin, nor did pretreatment with 50 micrograms bGH significantly alter GH response to clonidine stimulation, although the change in plasma GH with stimulation was only half that of controls. These data do not support a major autoregulatory effect on GH secretion in the sheep.
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PMID:Basal secretion of growth hormone in sheep is not influenced by GH feedback. 936 31

Studies of mutant mice that are growth hormone (GH)- and prolactin (PRL)-deficient have provided evidence that these pituitary hormones have trophic, as well as dynamic, feedback effects on the hypothalamic neurons that regulate GH and PRL secretion (1). This review examines further evidence, from those animals and from recent transgenic models, for GH and PRL effects on neuronal differentiation. Characterization of the Ames dwarf (Prop-1<df>) mutation and discovery of other genes important to pituitary differentiation reveal an expression sequence of transcription factors, Hesx1 (Rpx) to P-Lim to Prop-1 to Pit-1, that heralds influence on hypothalamic differentiation. Occasional expression of GH and PRL in the Ames dwarf pituitary may result from the "partial loss of function" nature of the Ames Prop-1 mutation. In transgenic mice with moderately or extremely elevated GH levels, neurons that regulate GH exhibit respective maximum and minimum expression and cell number in inhibitory somatostatin (SRIH) and in stimulatory GH-releasing hormone (GHRH). The phenomenon is inverted in GH-lacking dwarfs, and patterns of SRIH underexpression and GHRH overexpression are established early in postnatal development. The differentiation of PRL-inhibiting dopaminergic (DA) neurons is supported not only by PRL, but by human GH, which is lactogenic in rodents. Transgenic mice with peripherally expressed hGH have increased numbers of DA neurons, as opposed to the decreased DA population in PRL-deficient dwarf mice. Rats engineered to express hGH in GHRH neurons do not show this increase, whereas spontaneously GH-deficient dwarf rats show increased DA neuron number. These findings may be explained by feedback on neurons that co-express GHRH and DA. Current studies suggest that Snell (Pit-1<dw>) dwarf mice show a more severe and earlier DA neuron deficiency than Ames dwarfs, and that PRL feedback must occur prior to 20 days of postnatal age to maintain the DA neuronal phenotype. Insights into the mechanisms of GH and PRL effects on hypophysiotropic neurons include receptor localization on identified neuronal phenotypes, including intermediate neurons that mediate dynamic feedback, and elucidation of signal transduction pathways for GH and PRL in peripheral cell types. New transgenic models of altered GH, PRL, or receptor expression offer further study of neurotrophic effects.
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PMID:Pituitary hormones as neurotrophic signals: update on hypothalamic differentiation in genetic models of altered feedback. 1051 Feb 45

The bioequivalence of recombinant human growth hormone (rhGH) for reconstitution, at either 24 IU or 8 mg, and three strengths of liquid formulation of rhGH (5, 10 or 15 mg per 1.5 ml, hGH) was tested in two randomized, single-blind, four-period, crossover studies in healthy subjects. The study drugs were administered by subcutaneous injection at a dose of 2.5 mg rhGH/m(2)body surface area or as a fixed dose of 5 mg rhGH. Endogenous hGH release was suppressed by a continuous somatostatin infusion. The 90% confidence intervals for the estimated mean ratios of AUC(0-24 h)and C(max)(analysis of variance) between all products were within 80-125% in both studies. Also, no significant differences (P> 0.05; Wilcoxon signed rank test) were found between t(max)for the liquid formulations of rhGH. These data demonstrate that there is bioequivalence between rhGH for reconstitution and the liquid formulations of rhGH.
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PMID:Bioequivalence between ready-to-use recombinant human growth hormone (rhGH) in liquid formulation and rhGH for reconstitution. 1093 47

Since acromegaly is associated with high rates of comorbidities and increased mortality risk compared to the general population, over the last few years somatostatin analogues have been used to treat acromegaly patients who, following surgery, have not fulfilled cure criteria (basal hGH < 2.5 ng/ml, IGF-1 below normal ranges for age and sex and hGH < 1.0 ng/ml in the 120th min of the OGTT test). We assessed the efficacy of Octreotide LAR (OCT-LAR) in managing such patients. 72 patients underwent diagnostic tests to qualify them for Octreotide LAR treatment. Treatment efficacy evaluation was based on measuring the concentration of hGH and IGF-1 prior to and 3 and 12 months and performing control MRI 6 and 12 months after the beginning of OCT-LAR treatment. The dose of O ctreotide LAR was 20 mg/month, increased to 30 mg/month if unsatisfactory response was observed. We evaluated the efficacy of Octreotide LAR in 48 acromegaly patients (66.7% of 72 evaluated), in whom criteria of postsurgery cure were not fulfilled. 24 patients (33.3%) did not require further treatment. After 3 months of OCT-LAR treatment, hGH < 2.5 ng/ml was stated in 37.0% of patients, median value--3.4 ng/ml (IQR = 5.3), as compared to median value of 5.5 ng/ml (IQR = 5.6) before treatment (p < 0.05). After 3 months of treatment IGF-1 below normal ranges for age and sex was stated in 55.5% of patients, median value--336.8 ng/ml (IQR = 290.0), as compared to median value of 520.0 ng/ml (IQR = 351.0) prior to OCT-LAR treatment (p < 0.05). After 12 months hGH < 2.5 ng/l ml and IGF-1 below normal ranges for age and sex were found in 63.0% and 54.5% of patients, respectively. In control MRI recurrence, correlated with enhanced concentration of IGF-1, was stated in 7 patients (14.6%). Thus, we conclude that satisfactory acromegaly control, in terms of hGH and IGF-1 levels, was obtained in above 50% of patients treated with Octreotide LAR. Since in the studied group hGH secretion had achieved cure criteria after 3 months in 37.5% as compared to 63.0% after 12-months, assessment of OCT-LAR treatment should be extended over periods exceeding 3 months.
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PMID:[Evaluation of the efficacy of Octreotide LAR in the treatment of acromegaly--a yearly observation]. 1973 77

Acromegaly is a rare disease with insiduous onset of clinical, endocrine and local, manifestations, and therefore often delayed diagnosis. Acral enlargement like prognathism and a bulky sweaty handshake, hyperhidrosis and thickening of the skin are almost always present, and, because of the cardiorespiratory comorbidities mortality is threefold increased compared to the normal population. Measurement of hGH level > 1ng/mL after an oral glucose load and of elevated IGF-1 confirm the diagnosis. A pituitary macroadenoma can be shown by MRI in over 90 % of the patients, in less than 1 % an ectopic source of hGH or GHRH may be the cause. The aim of the treatment is to stop the hGH overproduction and to prevent complications. The treatment of choice is transsphenoidal surgery, often combined with pharmacological therapy with long-acting somatostatin analogs, pegvisomant and dopamine agonists, or gamma knife radiosurgery.
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PMID:[A gentle giant...]. 2110 88


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