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)

Growth hormone (GH) secretion in man is pulsatile and this pattern is regulated by both GH-releasing hormone (GHRH) and somatostatin. A large body of experimental evidence in both man and animals supports the model that bursts of GH secretion are mediated by a reduction of tonic hypothalamic somatostatin secretion. Our studies have been performed in normal subjects with frequent blood sampling for GH measurements (from 20-minute to 30-second intervals); the data have been analyzed by computer algorithms to objectively determine pulse characteristics and, in some studies, to estimate both pituitary secretion and clearance rates using deconvolution analysis. The studies include profiles of GH secretion in normal men and women in fed and fasted states; analysis of GH secretion during sleep; and administration of GHRH during different stages of sleep and after sleep deprivation. The variable GH response to exogenous GHRH and the attenuated response after 6 hours of GHRH infusion to GHRH, while not to hypoglycemia, as well as the pulsatile profile of GH secretion in response to continuous GHRH infusions (24 hours to 14 days), all support the thesis that it is hypothalamic somatostatin that determines the timing of bursts of GH secretion. This is further confirmed by the profile of GH secretion in a patient with ectopic GHRH secretion. Recently, we have initiated studies with the novel synthetic GH releasing hexapeptide, HisDTrpAlaTrpDPheLysNH2 (GHRP). Our studies show that it acts synergistically with GHRH. Several lines of evidence suggest that GHRP stimulates GH secretion independently of GHRH receptors and acts at both the hypothalamic and pituitary levels. It may act to functionally antagonize somatostatin.
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PMID:Physiological role of somatostatin on growth hormone regulation in humans. 197 18

Growth hormone (GH) secretory patterns are influenced by sex steroids, at least in part, through modulation of the secretion of hypothalamic somatostatin (SS) and GH-releasing hormone. Neurons in the periventricular nucleus (PeN) expressing the messenger RNA (mRNA) for SS are modulated by physiological levels of testosterone. However, it is uncertain whether testosterone's action is mediated directly by androgen receptor activation or indirectly through aromatization to estradiol and subsequent binding to the estrogen receptor. We examined this question by evaluating the effectiveness of 17 beta-estradiol and the nonaromatizable androgen, dihydrotestosterone (DHT), to mimic the effects of testosterone. Adult male rats were castrated and implanted subcutaneously with a Silastic capsule that contained either testosterone, 17 beta-estradiol or DHT, or a sham capsule. Intact animals were sham-operated. We used in situ hybridization to assess the effect of these treatments on SS mRNA signal levels in individual neurons of the hypothalamus. Following castration, SS mRNA content was reduced in cells of the PeN (intact, 195 +/- 12 grains/cell, vs. castrated, 139 +/- 4 grains/cell). Replacement with physiological levels of testosterone prevented the decline in SS mRNA signal levels (castrated testosterone-replaced, 214 +/- 15 grains/cell) as did replacement with the nonaromatizable androgen DHT (castrated DHT-replaced, 213 +/- 16 grains/cell). Treatment with 17 beta-estradiol failed to prevent the postcastration decline in SS mRNA content (castrated estrogen-replaced, 145 +/- 4 grains/cell). Castrated 17 beta-estradiol-treated animals were not significantly different from the castrated sham-treated animals (castrated, 139 +/- 4 grains/cell, vs. castrated estrogen-replaced, 145 +/- 4 grains/cell).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin messenger RNA in hypothalamic neurons is increased by testosterone through activation of androgen receptors and not by aromatization to estradiol. 197 39

The aim of this study was to assess the effects a long-acting somatostatin analogue (octreotide) had on the heart function of acromegalic patients. Five patients fulfilling clinical criteria of active acromegaly without symptoms of heart dysfunction, were treated with increased doses of octreotide (300, 600, 900, 1,200 and 1,500 micrograms/daily) over a period of six months. Growth hormone (GH) profiles were carried out during each different dose of octreotide. M-Mode, two dimensional and Doppler echocardiographic evaluation were performed both before and after treatment. Although the GH levels of all patients dropped after each increment of the octreotide, the responses were not homogeneous. Six months after the onset of treatment, echocardiographic studies revealed a significant reduction in the interventricular septum thickness (IVST) (p less than 0.05) and Doppler analyses showed an increase in the early diastolic transmitral flow velocity (p less than 0.05). Our results indicate that octreotide is capable of reversing acromegalic cardiopathy, since it not only reduces GH levels to within normal limits but improves left ventricular hypertrophy and distensibility without modifying contractility.
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PMID:Acromegalic cardiopathy improves after treatment with increasing doses of octreotide. 204 21

Growth hormone releasing factor (GRF) neurons in the arcuate nucleus of the hypothalamus and somatostatin (SRIF) neurons in the anterior periventricular region of the hypothalamus act to control the release of growth hormone from the anterior pituitary. To investigate the possibility that the growth-controlling functions of these cells might be compromised by injuries to the developing brain, it is important to know the details of the production and differentiation of these small, specialized cell groups. The overall pattern of cell production in the hypothalamus is known from autoradiographic studies with general nuclear stains, but no data are available on the birthdates (times of final mitoses) of GRF-producing cells. The present study was undertaken to determine when the GRF cells form. Counts of immunocytochemically identified GRF cells labeled on given days were taken from serial coronal sections through the hypothalamus of adult rats labeled on the 10th-17th days of gestation (day of finding a vaginal plug = day 1). As has been shown for the hypothalamus in general, the GRF cells showed a gradient of production from anterior to posterior. The peak of anterior cell proliferation was on day 13, middle cells on day 14, and posterior cells on day 15. These dates are 1 or 2 days earlier than those of GRF-negative cells in the same regions. No lateral to medial gradient of formation was seen in GRF cells. Rather, the laterally placed cells along the base of the brain and those surrounding the ventromedial nucleus formed simultaneously with the GRF cells of the arcuate nucleus. The birthdating results presented here are in agreement with the results of studies of teratogens which suggest that rat postnatal growth is reduced most severely by exposure to neurotoxic agents on days 12 or 13 of gestation. On the basis of data for the whole hypothalamus, such treatments would appear to be too early to interfere with cell production for the arcuate nucleus, but the timing fits the period of vulnerability as defined by the birthdates determined in the present study for the subpopulation of cells destined to produce GRF.
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PMID:Birthdates of the growth hormone releasing factor cells of the rat hypothalamus: an autoradiographic study of immunocytochemically identified neurons. 210 44

Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 micrograms/h) were maintained for 3 to 6 h whilst serial injections of GRF(1-29)NH2 (0.2-1 microgram) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat.
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PMID:Sex difference in growth hormone feedback in the rat. 211 94

We have studied the effect of somatostatin analogue (SMS 201-995) given as a subcutaneous injection on the growth and growth hormone secretion in seven tall children (two male; five female). SMS 201-995 was given in doses of 37.5 or 50 micrograms on a once or twice-daily regimen. Growth velocity decreased from a pretreatment median of 8.3 cm/year (range 5.5-12.2) to 3.0 cm/year (range 0.2-4.5) after 6 months treatment (Wilcoxon, P = 0.02). In three of the children therapy was discontinued for the next 6 months with restoration of growth rate to pretreatment values in two of the three. Growth hormone secretion decreased as a result of SMS 201-995 therapy although one child needed a twice-daily regimen to achieve long-term suppression. Final height measurements were reduced in four of five patients with an overall reduction between 1.1 and 6.3 cm and no change in the other. No effects of treatment on fasting glucose and insulin, glycosylated haemoglobin or serum thyroxine concentrations were observed. These preliminary studies suggest that SMS 201-995 may have a role in the management of the growth of tall children but the optimum mode of administration remains to be established.
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PMID:A preliminary report on the role of somatostatin analogue (SMS 201-995) in the management of children with tall stature. 218 61

Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.
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PMID:Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus. 219 45

Growth hormone (GH) secretion in patients with Cushing's syndrome is diminished to all the stimuli tested so far but the precise mechanisms through which this occurs are unknown. In order to investigate whether increased somatostatinergic tone might be responsible for this alteration, we studied the effect of pyridostigmine (120 mg p.o. at -60 min), which activates cholinergic synapses and thus suppresses hypothalamic somatostatin release on GH responses to GHRH (100 micrograms, i.v. at 0 min), in six patients with Cushing's syndrome. We found that while pyridostigmine markedly potentiated GH responses to GHRH, in all the normal subjects tested (n = 12), neither GHRH alone nor GHRH plus pyridostigmine elicited any increase in GH secretion in any of the patients with Cushing's syndrome. This suggests that chronic glucocorticoid excess induces marked alterations in the hypothalamic control of GH secretion.
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PMID:Effect of enhancement of endogenous cholinergic tone with pyridostigmine on growth hormone (GH) responses to GH-releasing hormone in patients with Cushing's syndrome. 222 84

Growth hormone (GH) is secreted in a pulsatile way during the whole life under the reciprocal influence of somatostatin and GH-releasing hormone (GHRH). It mediates many effects by stimulating production of insulin like growth factor I (IGF I) in liver and other tissues, but IGF I is also regulated by the nutritional state. Women secrete more GH than men, and older men and women less than young women. This suggests importance of estradiol in regulating secretion. Sex hormone effects are also demonstrated by the increment of GH and IGF I at puberty, which is an amplitude-modulated phenomenon. Classic metabolic studies have shown that patients with GH-deficiency retain more nitrogen in response to a given dose of exogenous hGH than normal subjects. The use of the stable isotope 15N has simplified such studies. In GH-deficient patients, there was with this technique a marked positive hGH-induced balance change. In girls with Turner syndrome (as example of subjects with normal GH-secretion), balance change was less marked with the same dose. Girls with Turner syndrome, who were given a double hGH-dose showed a response in the same range as that in the GH-deficient patients with the lower dose. A conclusion from this is that patients with normal GH-secretion need higher doses to obtain a similar response, than patients with GH-deficiency. The dosage in such patients will have to be selected individually, and needs to be about twice or three times as high as in GH-deficient patients.
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PMID:Assessment of growth hormone secretion in children. 225 28

A deconvolution analysis model to calculate pituitary growth hormone (GH) secretion rate from measured serum GH concentration has been developed. This uses an iterative method of 'curve-stripping' based on an estimate of the half-life. The model has been applied to serum GH profiles and demonstrates that GH secretion occurs in discrete bursts with quiescent periods between secretory episodes, an 'on-off' phenomenon. The model can clearly dissect complicated concentration profiles such as the serum GH concentration response to growth hormone releasing hormone. The estimate was derived from calculating the half-life of serum GH in 10 subjects following an intravenous bolus injection of 50 mU of biosynthetic human growth hormone (b-hGH) and following infusions of the exogenous hormone (3 mU/kg/h) for 15, 30, 60 and 180 min. Endogenous GH secretion was suppressed by a continuous infusion of somatostatin (1-14). An asymptotic relationship between the duration of GH infusion and the GH half-life was established. A half-life of 15.3 min was achieved after exposure to GH for 60 min and a maximum half-life of 15.7 min after 180 min exposure.
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PMID:The application of deconvolution analysis to elucidate the pulsatile nature of growth hormone secretion using a variable half-life of growth hormone. 238 25


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