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 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 The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system.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

Glucocorticoids have been shown to inhibit GH secretion in normal man when acutely and chronically administered in pharmacological amounts. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate the influence of glucocorticoids on the GH response to PD administered either alone or in combination with GHRH in normal adult subjects. Six healthy adult volunteers underwent six experimental protocols. They received 1) human (h) GHRH(1-29)NH2, 100 micrograms injected as an iv bolus; 2) cortisone acetate, 50 mg administered orally (po) 60 min before an hGHRH iv bolus injection; 3) PD, 120 mg administered po, 60 min before an hGHRH iv bolus injection; 4) PD and cortisone acetate, administered po 60 min before an hGHRH iv bolus injection; 5) PD, administered po 60 min before a saline iv bolus injection; 6) PD and cortisone acetate administered po 60 min before a saline iv bolus injection. Mean GH levels, peak GH levels, and GH area under the curves (AUCs) were significantly lower after GHRH + cortisone as compared to GHRH alone. However, these parameters were not significantly different after PD + GHRH + cortisone when compared to PD + GHRH and after PD + cortisone when compared to PD alone. We conclude that acute administration of pharmacological amounts of glucocorticoids cannot inhibit the GH response to PD alone or in combination with GHRH. Thus, we hypothesize that the inhibitory action of glucocorticoids on the GH response to GHRH in man may be mediated by an enhancement of either somatostatin release by the hypothalamus or somatostatin action on the pituitary.
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PMID:Pyridostigmine blocks the inhibitory effect of glucocorticoids on growth hormone-releasing hormone stimulated growth hormone secretion in normal man. 211 35

To determine the time onset of the growth hormone (GH) alteration in the genetically obese rat, we studied the in vivo and in vitro rat growth hormone releasing factor (rGRF(1-29)NH2)-induced GH secretion in 6- and 8-week-old lean and obese male Zucker rats. Under sodium pentobarbital anesthesia, rGRF(1-29)NH2 (GRF) was injected intravenously at two doses: 0.8 and 4.0 micrograms/kg b.w. Basal serum GH concentrations were similar in lean and obese age-matched animals. The GH response to both GRF doses tested was unchanged in 6-week-old obese rats as compared to their lean litter mates. In contrast, a significant decrease of the GH secretion in response to 4.0 micrograms/kg b.w. GRF was observed in the 8-week-old obese rats. The effect of GRF (1.56, 6.25 and 12.5 pM) was further studied in vitro, in a perifusion system of freshly dispersed anterior pituitary cells of lean and obese Zucker rats. Basal GH release was similar in the 6-week-old animal group. In contrast, it was significantly decreased in 8-week-old obese rats as compared to their lean litter mates. Stimulated GH response to 1.56 and 6.25 pM GRF was significantly greater in the 6-week-old obese group than in the age-matched control group. In contrast, the GH response to all GRF concentrations tested was significantly decreased in the 8-week-old obese rats as compared to their respective lean siblings. In 8-week-old obese rats, a decrease of GH pituitary content and an increase of hypothalamic somatostatin (SRIF) concentration were observed. Insulin and free fatty acid serum were significantly increased in 8-week-old obese rats. In contrast, lower insulin-like growth factor I serum levels were observed in the obese animals as compared to their lean litter mates. Finally, to further clarify the role of the periphery in the inhibition of GH secretion observed in the 8-week-old fatty rats, we exposed cultured pituitary cells of 8-week-old lean animals to 17% serum of their obese litter mates. A significant decrease of GRF-stimulated GH secretion of lean rat pituitary cells exposed to the obese serum was noted (P less than 0.05). This study demonstrates that, in the obese Zucker rat, an alteration of the GH response to GRF is evident by the 8th week of life. This defective GH secretion could be related to peripheral and central abnormalities.
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PMID:Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors. 213 33

We have treated eight pre-pubertal children with partial GH insufficiency with continuous subcutaneous infusions of GHRH(1-29)NH2 at a dose of 60 ng/kg/min for periods of up to 1 year. In five children treated for 1 year, mean growth velocity increased from 4.6 cm/year (range 4.4-5.2) to 7.0 cm/year (5.7-8.7) (P = 0.04). Three children treated for 3-6 months showed similar height velocity increases. A return to pretreatment growth rates was seen after cessation of treatment in all children. Twenty-four-hour GH profiles performed at intervals of 3 months showed sustained augmentation of pulsatile GH secretion without evidence of desensitization. The presence of pulsatile GH secretion during continuous GHRH administration provides strong evidence in man for the role of somatostatin in determining GH pulse frequency. The ability of the pituitary to respond to a supramaximal bolus of GHRH remained constant during the treatment. Continuous administration of GHRH(1-29)NH2 will become a practicable treatment when formulated into a sustained release or depot preparation. We have shown this to be an effective therapy for some short, slowly growing children. Further studies are required to establish the optimal dosage regimen.
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PMID:Continuous subcutaneous GHRH(1-29)NH2 promotes growth over 1 year in short, slowly growing children. 214 Jul 33

In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH.
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PMID:Impaired growth hormone (GH) response to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. 222 5

As part of a series of studies in which we are attempting to determine the roles of the lateral spinal (LSn) and lateral cervical (LCn) nuclei in somatic sensation, we have examined the fibers and terminals within these nuclei in the rat using the indirect immunofluorescence technique. Eleven antisera were used. Within the LSn, antisera against dynorphin 1-8 (DYN), substance P (SP), and Met-enkephalin (ENK) produced labeling of a large number of processes in all segmental levels examined. Processes labeled with these antisera frequently apposed the cell bodies and dendrites of LSn neurons. Antisera against somatostatin (SOM) and FMRF-NH2 (FMRF) labeled smaller numbers of processes within the LSn. Few, if any, processes in the LSn were labeled using antisera against serotonin, cholecystokinin octapeptide, oxytocin, neurotensin, corticotrophin-releasing factor, and vasoactive intestinal polypeptide. In contrast to the LSn, the LCn contained virtually no labeled processes irrespective of the antiserum employed. An area was found adjacent to the LCn in the medial portion of the dorsal lateral funiculus (DLf) of C2 that resembled the LSn in several of its anatomical characteristics: like the LSn, the medial portion of the C2 DLf contained small multipolar neurons; it was similar to the LSn in its medial-lateral extent; and following staining with each antiserum, the LSn and the medial DLf of C2 contained a similar number of labeled processes. The peptide-containing area in the medial DLf of C2 was found to be continuous with the LSn. We therefore propose that this region is a rostral extension of the LSn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical studies of the peptidergic content of fibers and terminals within the lateral spinal and lateral cervical nuclei. 241 May 76

Two calcium-activated neutral proteases (CAPI & II) were purified from human skeletal muscle by anion exchange, gel filtration and affinity (antipain-Sepharose and Blue Ultrogel A4R) chromatography. The enzymes were homogenous as judged by polyacrylamide gel electrophoresis, and have similar properties with the exception of the Ca2+ concentration required for optimum activity (CAP I = 0.1 mM; CAP II = 1 mM). Both enzymes hydrolysed a wide variety of neuropeptides. In six cases, the products were separated and identified by hplc and amino acid analysis. Neurotensin was hydrolysed at Tyr3-Glu4; dynorphin1-13 at Arg8-Arg9; LH-RH at Gly6-Leu7; CCK-8 at Phe8-NH2, substance-P at Met10-NH2; somatostatin at Thr10-Phe11. Although differences in the rates of neuropeptide degradation were noted for the two CAP's the specificity was the same for these six peptides. It is suggested that conformational requirements may be more important than side chains adjacent to the cleavage site in directing the specificity of CAP.
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PMID:Specificity of neuropeptide degradation by two calcium-activated neutral proteases from human skeletal muscle. 241 Jul 57

The arcuate nucleus surrounds the ventral part of the third ventricle and contains densely packed small neurons with 1-3 dendrites. At least fifteen transmitters and neuropeptides have been found in perikarya of arcuate neurons. Each transmitter and neuropeptide have a characteristic distribution. In many cases distributions overlap (for example, dopamine and somatostatin, dopamine and neurotensin, neuropeptide Y and somatostatin) and alpha-MSH and beta-endorphin seem to have identical distributions but there are also distinctive neuronal populations containing only one of the described transmitters or neuropeptides (neuropeptide Y and alpha-MSH). Studies show extensive colocalization of dopamine and neurotensin and sparse colocalization of dopamine and GABA, neuropeptide Y and FMRF-NH2 and neuropeptide Y and somatostatin. Colocalization does not seem to be the rule in the arcuate, however, it is possible that colocalization may vary with the physiological state or sex of the animal. It also should be noted that our techniques may not be sensitive enough. To study efferent projections as a possible organizing principle within the arcuate, retrograde fluorescent tracing was combined with transmitter and neuropeptide immunohistochemistry. Mainly NPY and alpha-MSH neurons were studied and both peptides are present in projections to the preoptic area as well as to the midbrain periaqueductal gray. Some arcuate neurons were found to have collateral axons to both these areas. The arcuate communicates primarily with the pituitary gland, hypothalamus, limbic system, midbrain periaqueductal gray and autonomic nuclei of the brain stem. In this way, the arcuate may be involved in integrating emotional, sensory, vegetative homeostatic and autonomic functions with endocrine functions.
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PMID:Anatomy and physiology of the neuroendocrine arcuate nucleus. 241 5

The effects on pancreatic responses of highly potent cyclic hexapeptide (cyclo (N-Me-Ala-Phe-D-Trp-Lys-Thr-Phe)) (Veber analog) and octapeptide analogs of somatostatin such as D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (SMS 201-995), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) have been compared with somatostatin tetradecapeptide (SS-14) and atropine. The parameters evaluated were pancreatic responses to secretin and meat feeding in conscious dogs with chronic pancreatic fistula and amylase release from the dispersed pancreatic acini. The analogs were administered intravenously or intraduodenally. The cyclic hexapeptide and octapeptide analogs, given iv in graded doses against a constant background stimulation with secretin, produced similar and dose-dependent inhibition of pancreatic HCO3- and protein secretion. Analogs RC-121, RC-160, and the Veber analog were about two to four times more active than SS-14 in suppressing HCO3- secretion and equipotent in reducing protein secretion, but SMS 201-995 was only about half as potent as somatostatin in inhibiting HCO3-. RC-160 was effective in inhibiting secretin-induced protein secretion at lower doses than other analogs. In tests with feeding, SMS 201-995, the Veber analog, RC-121, and RC-160 were more potent inhibitors of exocrine pancreatic secretion of HCO3- and protein and exhibited more prolonged inhibitory effects than SS-14. The Veber analog, RC-121, and RC-160 were also more effective after intraduodenal administration. Atropine also caused significant inhibition of both HCO3- and protein responses to secretin and meal feeding. All four analogs decreased the postprandial insulin and pancreatic polypeptide release to a similar degree as SS-14. Neither SS-14 nor the analogs tested significantly affected basal or caerulein-, gastrin-, secretin-, or bethanechol-stimulated amylase release from the dispersed canine pancreatic acini. Atropine reduced amylase release induced by bethanechol, but not that stimulated by caerulein, gastrin, or secretin. This indicated that the analogs, as somatostatin, are ineffective as secretory inhibitors in vitro. We conclude that cyclic hexapeptide and octapeptide analogs are more potent and longer acting inhibitors of pancreatic secretion than somatostatin-14 in vivo.
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PMID:Comparison of somatostatin and its highly potent hexa- and octapeptide analogs on exocrine and endocrine pancreatic secretion. 244 2

In an attempt to clarify the regulatory role in GH secretion of central alpha-adrenergic and dopaminergic mechanisms, the effects of iv administration of alpha 1- and alpha 2-adrenergic antagonists and dopaminergic antagonists were investigated in undisturbed conscious male rabbits. During a 6-h observation period (1030-1630 h), control animals demonstrated spontaneous pulsatile GH secretion with mean (+/- SEM) 6-h GH levels of 6.49 +/- 0.54 ng/ml (n = 16). Intravenous injection of yohimbine (YOM; an alpha 2-antagonist), chlorpromazine (CPZ), and haloperidol (HAL; dopamine and alpha-adrenergic antagonists) completely suppressed this pulsatile GH secretion (mean 6-h GH levels, 2.98 +/- 0.24, 3.48 +/- 0.24, and 2.91 +/- 0.29 ng/ml, respectively; P less than 0.001), whereas prazosin (an alpha 1-antagonist), pimozide (a selective dopamine antagonist), sulpiride, and YM-09151-2 (YM; D2-specific antagonists) failed to affect the GH secretory pattern (mean 6-h GH levels, 6.61 +/- 0.73, 6.71 +/- 0.56, 5.44 +/- 0.44, and 6.87 +/- 1.44 ng/ml, respectively). While an iv injection of 2 micrograms synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) induced GH rises in prazosin-, HAL-, pimozide-, sulpiride-, and YM-treated rabbits as well as control rabbits, YOM and CPZ completely abolished these GH responses to hGRF injection. An iv injection of 10 ml antisomatostatin gamma-globulin caused a prompt and transient GH rise, followed by a sustained elevation of GH trough levels in normal control rabbits. YOM treatment completely abolished this highly oscillated GH release. However, suppression by YOM or CPZ of hGRF-induced GH rises was significantly reversed by iv administration of 10 ml antisomatostatin gamma-globulin. Therefore, the inhibitory effect of YOM and CPZ on both episodic GH release and hGRF-induced GH rises is due to the enhanced release of somatostatin, with a simultaneous suppression of endogenous GRF. On the other hand, HAL, possessing a weaker alpha-blocking action than CPZ, blunted pulsatile GH secretion, but only modestly suppressed hGRF-induced GH rises. These results suggest the following. 1) Central alpha 2-adrenergic mechanisms play a more important role in the regulation of GH secretion than alpha 1-adrenergic mechanisms in the rabbit as well as in other species. 2) The alpha 2-adrenergic blockade causes suppression of the release of hypothalamic GRF and enhanced release of endogenous somatostatin, thereby suppressing GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. 247 28


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