Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acromegalic patients do not respond with the same degree of growth hormone (GH) inhibition to long-term therapy with the somatostatin analogue SMS 201-995. In order to find a parameter predictive of the effectiveness of the drug, we studied in twelve patients with active acromegaly the relationship between paradoxical GH response to gonadotropin- and thyrotropin-releasing hormone (GnRH and TRH) and GH inhibition after a single standard dose (100 micrograms) of SMS 201-995. Four hours after the subcutaneous injection of the analogue, only those patients who responded to the releasing hormones demonstrated a persistent inhibition of somatotropic cell function. SMS 201-995 appears an effective means for suppressing the elevated GH levels in active acromegaly. Its activity may be more pronounced and its use more beneficial in those patients who react paradoxically to GnRH and TRH.
 ...
PMID:Paradoxic elevation in serum GH by hypothalamic releasing hormones predicts GH response to acute SMS 201-995 administration. 190 62

We studied the effect of histamine on serum prolactin and thyrotropin (TSH) levels in male rats with anterolateral hypothalamic deafferentation of hypothalamic connections or anterolateral cut (ALC). The success of ALC was confirmed by immunohistochemistry of somatostatin (SRIF) in the medial basal hypothalamus. ALC did not affect basal prolactin or TSH levels. Thyrotropin-releasing hormone (TRH, 200 ng/rat, i.p.) did not affect prolactin secretion either in sham-operated or ALC rats. In sham-operated rats intracerebroventricularly administered histamine increased significantly prolactin levels. Hypothalamic deafferentation abolished the effect of histamine on prolactin levels. TRH increased significantly serum TSH levels both in sham-operated controls and ALC rats. In the latter, however, the TSH-secretory response to TRH was significantly (p less than 0.05) larger compared to the controls. Intracerebroventricularly infused histamine (2 micrograms/rat) did not change the TRH-induced TSH secretion in either group of rats. These results show that (1) the effect of histamine on prolactin secretion is mediated through nerve tracts which are destroyed by ALC, and (2) cutting of afferent TRH (through sensitization) and SRIF fibers (through lacking inhibition) entering medial basal hypothalamus may both contribute to the enhanced TSH response to exogenous TRH.
 ...
PMID:Anterolateral hypothalamic deafferentation inhibits histamine-induced prolactin secretion and potentiates TRH-induced thyrotropin secretion in male rats. 194 13

Absorption of somatostatin (SRIF) specific antibodies from colostrum of ewes actively immunized against SRIF may improve growth rate of the neonatal lamb by neutralizing the inhibitory effects of SRIF on pituitary and thyroid function. Growth and endocrine parameters in the offspring of SRIF immunized (SI) and control (C) crossbred ewes were examined. Lamb weight was recorded at birth and twice each week to 24 days of age. Blood samples were collected prior to first suckle and twice each week. At 21 to 24 days of age, in separate experiments, lambs were infused with glucose (0.29 g/kg), arginine (0.25 g/kg) or thyrotropin-releasing hormone (TRH; 0.33 microgram/kg). A strong correlation (R = 0.88; P less than .01) was observed between anti-SRIF titre in the ewe at parturition and in the lamb at 3 days of age. No effect on lamb birth weight (SI 4.28 +/- 0.27 kg; C 4.35 +/- 0.23 kg) was observed. At 24 days of age cumulative gain in SI lambs (5.4 +/- 0.32 kg) was greater (P less than .05) than in C lambs (4.5 +/- 0.32 kg). The growth hormone secretory responses to glucose or arginine were not affected by treatment. Plasma IGF-I, plasma thyroxine (T4) and the plasma thyrotropin and T4 responses to TRH were not different between treatments. Plasma triiodothyronine (T3) was higher (P less than .05) in SI (2.46 +/- .10 ng/ml) than in C (2.01 +/- .05 ng/ml) lambs, however, the plasma T3 response to TRH was lower in SI lambs. Plasma glucose (mg/dl) was higher (P less than .05) in SI (118.4 +/- 1.7) than in C (106.0 +/- 4.0) lambs. Plasma insulin was not affected by treatment. Increased plasma T3 and glucose concentrations during SRIF immunoneutralization in the neonate lamb may be important factors contributing to the growth response observed.
 ...
PMID:Effect of immunization against somatostatin in the pregnant ewe on growth and endocrine status of the neonatal lamb. 197 64

We examined the effect of prior exposure to somatostatin (SRIH) on its inhibition of GH and TSH responses to GHRH and TRH stimulation to determine whether SRIH desensitization has physiological significance in man. Six men received GHRH (1 microgram/kg, iv) and TRH (0.3 microgram/kg, iv) 20 min after starting a saline or SRIH (5.5 ng/kg/min, iv) infusion and again 6 h later. Hormone responses were quantified by measuring the area under the curve, corrected for GH concentration at injection time. Similar results were obtained when GH responses were quantified by measuring the hormone secretory rate using the program Detect. Plasma GH and TSH responses to the two GHRH and TRH injections during saline were similar. However, the effects of prior exposure to SRIH were hormone specific. SRIH blunted GH responses to GHRH at 20 min (1609 +/- 286 micrograms/L.min vs. 451 +/- 224), but did not significantly inhibit the responses 6 h later (1422 +/- 410 micrograms/L.min vs. 1000 +/- 302). In contrast, SRIH inhibition of TSH responses to the two TRH injections was similar (first, 946 +/- 201 micrograms/L.min vs. 700 +/- 148; second, 813 +/- 175 micrograms/L.min vs. 562 +/- 66). We next used these results to study whether the previously reported attenuation of GH responses to repeated GHRH stimulation at 2-h intervals is mediated by SRIH. Eight men received GHRH (1 microgram/kg, iv) 380 min after starting a saline or SRIH (5.5 ng/kg/min, iv) infusion or 90 min after starting a primed (5 mg, iv) infusion of propranolol (80 micrograms/min, iv) and again 2 h later. As in the first protocol, GH responses to GHRH were not inhibited when preceded by a 6-h SRIH infusion. However, the 6-h SRIH infusion resulted in a partial restoration of plasma GH responses to the second GHRH injection (saline infusion: first, 1429 +/- 342 micrograms/L.min; second, 254 +/- 75; SRIH infusion: first, 1042 +/- 247 micrograms/L.min; second, 468 +/- 105). beta-Blockade by propranolol resulted in enhanced GH responses to GHRH, but did not prevent the attenuation of GH responses to the second GHRH injection (first, 1937 +/- 366 micrograms/L.min; second, 614 +/- 99). The desensitization to SRIH inhibition of GH responses to GHRH after a 6-h SRIH infusion provides evidence of physiological consequences of SRIH receptor down-regulation. The impaired GH responses to repeated GHRH stimulation are mediated at least in part by enhanced SRIH secretion, which appears independent of a beta-adrenergic mechanism.
 ...
PMID:Impaired inhibitory effects of somatostatin on growth hormone (GH)-releasing hormone stimulation of GH secretion after short term infusion. 197 20

[125I-Tyr1]-Somatostatin (SRIF)-binding sites were demonstrated on crude plasma membrane preparations from chicken pituitary glands. These binding sites were saturable and of high affinity (dissociation constant less than 1.0 nM) and low capacity (maximal binding capacity less than 200 fmol/mg protein) and were specific for SRIF moieties. The number and affinity of these binding sites in the caudal lobe of the pituitary, in which somatotrophs predominate, were similar to those in the cephalic lobe, in which lactotrophs and thyrotrophs are confined. Gonadotrophs are present in the caudal lobe, but whereas exogenous SRIF inhibited secretagogue-induced GH release from incubated pituitary glands, it had no effect on basal or secretagogue-induced LH release. The half-maximal binding of SRIF to the caudal lobe membranes (3 nM) was similar to that required for half-maximal suppression of TRH-induced GH release, suggesting a role for these binding sites in the regulation of GH secretion in birds.
 ...
PMID:Somatostatin binding to chicken adenohypophysial membranes. 197 35

TRH is present in human normal pituitaries and in pituitary adenomas. In this study we demonstrated that the same tissues can release TRH in vitro. Fragments from seven normal pituitaries (10-15 mg/syringe) and dispersed cells from eight prolactinomas, four GH-secreting and two nonsecreting adenomas (1-3 x 10(6) cells/syringe) were perifused using a Krebs-Ringer culture medium. After 1 h of equilibration the perifusion medium was collected every 2 min (1 mL/fraction) for 3 h. TRH, PRL, and GH were measured by RIA under basal conditions and in the presence of 10(-10) to 10(-6) mol/L dopamine (DA), alone or concomitant with haloperidol, or in the presence of 10(-10) or 10(-6) mol/L somatostatin. Both normal pituitary fragments and pituitary adenomatous cells (from all types of adenomas studied) spontaneously released TRH in vitro. TRH was detected in the perifusion medium either immediately after the end of the equilibration period or 30-60 min later. The molecular identity of TRH was assessed by high pressure liquid chromatography. There was no difference in the profile and the rate of TRH secretion between normal and tumoral tissues, and no correlation was found between the level of TRH release and that of PRL or GH secretion. DA stimulated TRH release from normal pituitaries and from PRL- and GH-secreting adenomas at doses as low as 10(-10) mol/L. A concomitant decrease in PRL and GH release was observed from adenomatous cells and in one case of normal tissue. Haloperidol (10(-7) mol/L) antagonized the effect of 10(-8) mol/L DA on both TRH and PRL secretion in normal pituitary and in prolactinomas. DA had no effect on TRH release from two nonsecreting tumors. The amounts of TRH released during 1 h of perifusion were 60-1640 pg/2 mg wet wt tissue in normal pituitaries and 54-2174 pg/10(6) cells in adenomas; these values were very high compared to those precedently reported within the tissues. These results indicate that pituitary cells can release TRH in vitro and suggest that TRH might be synthesized in situ. We suggest that TRH could act on pituitary hormone secretion and/or cell proliferation via a paracrine and/or an autocrine mechanism.
 ...
PMID:Normal and adenomatous human pituitaries secrete thyrotropin-releasing hormone in vitro: modulation by dopamine, haloperidol, and somatostatin. 197 64

The i.c.v. administration of 0.1 or 10 micrograms ovine (o)GH to 12- to 16-week-old hypothyroid chickens of a sex-linked dwarf (SLD) strain suppressed the basal plasma GH concentrations, measured 24 h afterwards. The GH response of the oGH-injected SLDs to TRH was suppressed, in a dose-related way, in comparison with that induced by TRH in birds given control injections (10 micrograms) of bovine serum albumin (BSA). Basal circulating concentrations of GH in euthyroid K strain birds of the same age were even lower than in the SLDs following injection of 10 micrograms oGH, and were not further reduced by oGH administration. The GH response to TRH in the K strain birds injected i.c.v. with 0.1 or 10 micrograms oGH was, nevertheless, suppressed in comparison with the BSA-injected K strain controls. The i.c.v. administration of oGH also suppressed circulating concentrations of LH and the LH response to TRH in the K strain birds. Twenty-four hours after i.c.v. administration of oGH (10 micrograms), the somatostatin (SRIF) content in the medial basal hypothalamus of 8-week-old euthyroid cockerels was greater than that in BSA (10 micrograms)-injected controls. At the same time, the binding of [3H]3-methyl-histidine2-TRH to the pituitary caudal and cephalic lobes of GH-injected birds was less than that in the controls. These results suggest that GH regulation in avian species is partly mediated by an inhibitory short-loop mechanism (mediated by hypothalamic SRIF and a down-regulation of pituitary TRH-binding sites) that suppresses basal and secretagogue-induced GH release.
 ...
PMID:Short-loop inhibition of thyrotrophin-releasing hormone-induced growth hormone secretion in fowl. 197 33

In the neonatal period of the rat, pancreatic thyrotropin-releasing hormone content decreases and the sensitivity of insulin secretion to glucose increases. In adult rat islets, TRH inhibits glucose-induced insulin release. The aim of this study was to investigate whether a high TRH content and release can be part of the explanation for the functional immaturity of neonatal islets. For that purpose, we have measured the tissue content and the secretion of immunoreactive insulin, glucagon, somatostatin and TRH in islets from 21.5-day-old rat fetuses cultured for up to one week. Insulin, glucagon and somatostatin content increased during one week of culture in the presence of 11.1 mmol/l glucose. The TRH content decreased during culture, but did not equal adult values. Insulin, glucagon and somatostatin responses to glucose were present after one week of culture. Glucose had no effect on TRH release in cultured fetal islets, but inhibited TRH release in adult islets. We conclude that glucose can stimulate insulin secretion without inhibiting TRH release, but that a decrease in islet TRH content and a sensitization of TRH secretion to glucose may be important in the full maturation of fetal pancreatic islets.
 ...
PMID:Insulin, glucagon, somatostatin, and thyrotropin-releasing hormone content and secretion by perifused fetal rat islets during culture. 197 58

Somatostatin (SS-14; growth hormone-release inhibiting hormone) was infused into eight patients with non-toxic sporadic goiter and into eleven normal control subjects. Each patient was given 150 microgram(s) of somatostatin as an intravenous bolus and 350 microgram(s) by infusion over a period of 60 minutes. Somatostatin did not lower the basal TSH levels as compared to the pre-infusion levels in this type of goiter, but produced a decrease in the TSH response to TRH during and after the infusion.
 ...
PMID:Effect of Somatostatin on TSH levels in non-toxic sporadic goiter. 198 67

The TRH secretory responsiveness of the pancreatic islet cell clusters from newborn rat in organ culture was studied. Basal TRH secretion was stable over a 9-day period. The response to various secretagogues was tested on day 4. TRH secretion was stimulated by high potassium-induced depolarization and also through both cAMP and protein kinase-C dependent pathways. Like insulin, TRH release was stimulated by glucose and arginine and inhibited by somatostatin. These data suggest the existence of a common mechanism for TRH and insulin secretion by the pancreatic beta-cells.
 ...
PMID:Regulation of TRH release by the cultured neonate rat pancreas. 198 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>