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)

TRH is synthesized in the islets of Langerhans and was found in the perfusate of isolated rat pancreas. In the present study, designed to determine the role of endogenous TRH, we first characterized chromatographically the identity of immunoreactive TRH with synthetic pGlu-His-Pro-NH2. Since endogenous TRH secretion may mask the effects of exogenous TRH, we performed, in parallel to dose-response studies, immunoneutralization experiments using anti-TRH serum to neutralize the endogenous TRH secretion from isolated perfused rat pancreas. The data indicate that exogenous TRH enhances basal glucagon secretion; inversely, anti-TRH serum inhibits glucose plus arginine-induced glucagon secretion and produces a concomitant slight inhibition of somatostatin secretion. The present study shows a physiological contribution for endogenous TRH as a local modulator of intraislet hormone regulation; from these observations, we postulate a direct effect of pancreatic TRH on glucagon-containing (alpha) cell secretion, which, in turn, may produce the fluctuation in somatostatin secretion. Local TRH secretion provides a model for positive feedback regulation of glucagon secretion, frequently associated with diabetes.
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PMID:Antithyrotropin-releasing hormone serum inhibits secretion of glucagon from isolated perfused rat pancreas: an experimental model for positive feedback regulation of glucagon secretion. 163 22

To determine the mechanism underlying pulsatile TSH secretion, 24-h serum TSH levels were measured in three groups of five healthy volunteers by sampling blood every 10 min. The influence of an 8-h infusion of dopamine (200 mg), somatostatin (500 micrograms), or nifedipine (5 mg) on the pulsatile release of TSH was tested using a cross-over design. The amount of TSH released per pulse was significantly lowered by these drugs, resulting in significantly decreased mean basal TSH serum levels. However, pulses of TSH were still detectable at all times. The TSH response to TRH (200 micrograms) tested in separate experiments was significantly lowered after 3 h of nifedipine infusion compared to the saline control value. Nifedipine treatment did not alter basal, pulsatile, or TRH-stimulated PRL secretion. The persistence of TSH pulses under dopamine and somatostatin treatment and the blunted TSH responses to nifedipine infusion support the hypothesis that pulsatile TSH secretion is under the control of hypothalamic TRH. The 24-h TSH secretion pattern achieved under stimulation with exogenous TRH in two patients with hypothalamic destruction through surgical removal of a craniopharyngioma provided further circumstantial evidence for this assumption. No TSH pulses and low basal TSH secretion were observed under basal conditions (1700-2400 h), whereas subsequent repetitive TRH challenge (25 micrograms/2 h to 50 micrograms/1 h) led to a pulsatile release of TSH with fusion of TSH pulses, resulting in a TSH secretion pattern strikingly similar to the circadian variation. These data suggest that pulsatile and circadian TSH secretions are predominantly controlled by TRH.
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PMID:Hypothalamic regulation of pulsatile thyrotopin secretion. 167 Jul 79

Control of growth hormone (GH) and prolactin (PRL) release was investigated in hypophysial stalk-transected (HST) and stalk-intact pigs by determining the effects of analogs of GH-releasing factors (GHRF), somatostatin (SRIF), arginine, thyrotropin-releasing hormone, alpha-methyl-rho-tyrosine, and haloperidol. HST and control gilts were challenged with intravenous injections of human pancreatic GHRF(1-40)OH, thyrotropin-releasing hormone, and analogs of rat hypothalamic GHRF. HST animals remained acutely responsive to GHRF by releasing 2-fold greater quantities of GH than seen in controls. This occurred in spite of a 38% reduction in pituitary gland weight and a 32 and 55% decrease in GH concentration and total content. During SRIF infusion, GH remained at similar basal concentrations in HST and control gilts, but increased immediately after stopping SRIF infusion only in the controls. Releasable pituitary GH appears to accumulate during SRIF infusion. GHRF given during SRIF infusion caused a 2-fold greater release of GH than seen in animals receiving only GHRF. Arginine increased (P less than 0.05) GH release in controls, but not in HST gilts, which suggests that it acts through the central nervous system. Basal PRL concentrations were greater (P less than 0.05) in HST gilts than in control gilts. TRH acutely elevated circulating PRL (P less than 0.001) in HST gilts, suggesting that it acts directly on the pituitary gland. Haloperidol, a dopamine receptor antagonist, increased circulating PRL in controls but not in HST animals. alpha-Methyl-rho-tyrosine did not consistently increase circulating PRL, however, suggesting that it did not sufficiently alter turnover rate of the tyrosine hydroxylase pool. The results indicate that the isolated pituitary after HST remains acutely responsive to hypothalamic releasing and inhibiting factors for both GH and PRL release in the pig.
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PMID:Growth hormone and prolactin secretion in hypophysial stalk-transected pigs as affected by growth hormone and prolactin-releasing and inhibiting factors. 167 Dec 98

1. Basal circulating growth hormone (GH) concentrations in sex-linked-dwarf (SLD) chickens were unaffected by the intracerebroventricular (icv) injection of 10, 50 or 100 micrograms somatostatin (SRIF). 2. The GH response to systemic thyrotropin-releasing hormone (TRH; 10 micrograms/kg, iv) was, however, 'paradoxically' enhanced 20 min after icv SRIF administration. 3. A lower dose (1.0 micrograms) of SRIF had no effect on basal or TRH-induced GH release. 4. High-titre SRIF antisera (4 microliters) also had no acute effect on basal plasma GH concentrations, but augmented the GH response to TRH challenge. 5. SRIF would appear to act at central sites to modulate stimulated GH secretion in SLD chickens.
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PMID:Central somatostatinergic regulation of growth hormone secretion in dwarf chickens. 167 68

The role of dopaminergic agents (DA) in the regulation of growth hormone (GH) secretion was investigated in patients with untreated acromegaly. TRH (0.5 mg iv), bromocriptine (Br) (2.5 mg orally) or L-Dopa (500 mg orally) loading tests were performed, and serum levels of TSH, GH and prolactin (PRL) were measured. Patients were defined as responders to TRH when peak TSH level after TRH test was higher than 5 microU/ml. Br or L-Dopa was considered to be effective when serum GH or PRL levels were suppressed more than 50% of the basal value. The patients were classified into large adenoma group with suprasellar extension or cisternal herniation (L group, n = 7) and intrasellar small adenoma group (S group, n = 11) which was further divided into TRH responder (Sr group, n = 4) and TRH non-responder with suppressed TSH (Ss group, n = 7). Br was effective in 7 or 100% of 7 patients in the Ss group but only in one or 25% of 4 patients in the Sr group. Br was also effective in 5 or 71% of 7 patients in the L group, although most of them were responders to TRH. Percent inhibition of serum GH levels by Br was significantly higher in the Ss group (82.3 +/- 12.3%, p less than 0.001) and in the L group (64.7 +/- 20.5%, p less than 0.05) compared with that in the Sr group (29.3 +/- 21.6%). Suppression of serum GH level by L-Dopa was also observed in the Ss group. In contrast to the difference in the response of GH, serum PRL level was equally suppressed by Br or L-Dopa in each group. Suppression of TSH by administration of exogenous T4 had no effect on the GH suppression effect of Br in the Sr group. Considering the dual effects of DA to enhance growth hormone-releasing hormone (GHRH) secretion in the hypothalamus and to suppress GH secretion in the pituitary gland, these findings suggest that the paradoxical effect of DA to suppress serum GH level is observed when the hypothalamo-pituitary axis is disturbed mechanically by large adenoma in the L group or functionally in the Ss group probably due to enhanced secretion of somatostatin which suppresses TSH secretion and impairs the effect of GHRH.
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PMID:[The relationship between TSH response to TRH and GH response to dopaminergic agents in patients with acromegaly]. 167 20

To determine the effect of thyroid status on proTRH-derived peptide processing and secretion, the content and release of TRH and prepro-TRH25-50 (PYE27), as well as somatostatin (SRIF) from median eminence (ME) or olfactory lobe (OL) tissue was studied in the rat. In hypothyroid animals treated by thyroidectomy (Tx), the ME content of TRH and PYE27 was reduced by more than 50%; further, when compared with euthyroid controls there was a significant 2-fold enhancement of the in vitro release of these peptides from ME fragments in response to depolarizing concentrations (60 mM) of potassium. Hyperthyroidism (T4 treatment) caused either no change or an increase in the ME content of these peptides and their response to K+ in vitro did not differ from control animals. The OL content of TRH and PYE27 was unaffected by thyroid status. SRIF levels in both ME and OL as well as in vitro secretion from the ME did not change with either Tx or T4 treatment. The ratio of TRH/PYE27 secretion throughout release and content studies remained stable at 3:1 to 4:1. These findings support the view that TRH in the hypothalamus but not OL is regulated by thyroid hormone. In this location hypothyroidism enhances not only pro TRH synthesis but also release of TRH and another proTRH-derived peptide. The consistent ratio of TRH/PYE27 suggests that regulation of TRH production by thyroid hormone occurs predominantly at the transcriptional level and not through posttranslation processing.
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PMID:Hypothyroidism reduces content and increases in vitro release of pro-thyrotropin-releasing hormone peptides from the median eminence. 167 96

Patterns of prolactin release were examined using stimulating and inhibiting agents. Primary cultured pituitary cells primed with oestrogens were used for perifusion experiments. TRH (100 nmol/l) increased the peak prolactin concentration to 360% of the basal concentration, while TRH, under inhibition by 1 nmol somatostatin/l, raised the peak prolactin concentration to 185% of the basal levels. When the somatostatin concentration was increased to 10, 100 and 1000 nmol/l, TRH still stimulated prolactin release to 128%, 121% and 140% respectively, indicating that concentrations of somatostatin of 10 nmol/l or higher did not further suppress the stimulatory effect of TRH. TRH (1 mumol/l) stimulated prolactin release under the influence of 0 (control), 1, 10, 100 and 1000 nmol dopamine/l (plus 0.1 mmol ascorbic acid/l) to 394, 394, 241, 73 and 68% of the basal concentration respectively, showing that the dopamine concentrations and peak prolactin concentrations induced by TRH have an inverse linear relationship in the range 1-100 nmol dopamine/l. The stimulatory effect of dibutyryl cyclic AMP (dbcAMP) on prolactin release was also tested. The relationship between dbcAMP and somatostatin was similar to that between TRH and somatostatin. When adenohypophyses of male rats were used for perifusion experiments, somatostatin (100 nmol/l) did not inhibit basal prolactin release from the fresh male pituitary in contrast with the primary cultured pituitary cells, but dopamine (1 mumol/l) effectively inhibited prolactin release. In conclusion, (1) oestrogen converts the somatostatin-insensitive route into a somatostatin-sensitive route for basal prolactin release, (2) TRH-induced prolactin release passes through both somatostatin-sensitive and -insensitive routes, (3) dopamine blocks both somatostatin-sensitive and -insensitive routes and (4) cAMP activates both somatostatin-sensitive and -insensitive routes.
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PMID:Somatostatin partially impedes the stimulatory effects of thyrotrophin-releasing hormone and dibutyryl cyclic AMP on prolactin release: prolactin release through multiple routes. 167 1

The present study was carried out to examine the role of endogenous dopamine and somatostatin in the mechanisms involved in the restricted feeding-induced inhibition of TSH secretion in rats. GH secretion was examined in parallel. Restricted feeding by 50% or 75% was associated with a decrease in the pituitary and circulating levels of TSH and GH in both untreated and TRH-treated groups (p less than 0.001), the changes being proportional to the feeding level. Intravenous injections of the dopamine antagonists, domperidone or haloperidol, failed to affect the magnitude of the differences in plasma TSH and GH levels among control and food-restricted groups, indicating that dopaminergic mechanisms had little effect on the regulation of TSH and GH secretion during restricted feeding in rats. Cerebroventricular injection of somatostatin anti-serum resulted in a marked increase in plasma TSH and GH levels in all the experimental groups (p less than 0.001). The increase in plasma GH and TSH induced by somatostatin anti-serum was greater in rats fed a 25% diet than in either controls or rats fed 50% of the diet; the values for the latter two groups were also different (p less than 0.001). The decreased TSH and GH values in somatostatin anti-serum-treated food restricted rats as compared with those in control animals on somatostatin anti-serum or normal rabbit serum can probably be attributed to the decreased available pituitary TSH and GH pools. The data indicate that long-term restricted feeding affects anterior pituitary function in rats, presumably reflecting alterations in the secretion of an inhibiting hormone, somatostatin.
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PMID:The role of somatostatin and/or dopamine in basal and TRH-stimulated TSH release in food-restricted rats. 168 Feb 65

Adenosine is a potent paracrine/autocrine feedback inhibitor of cell activation in a variety of tissues. Adenosine action was studied in pituitary cells, in which spontaneous electrical activity causes characteristic oscillations of the cytosolic free Ca2+ concentration, [Ca2+]i. Cells of the GH3B6 rat pituitary tumor line were studied by microspectrofluorimetry using the Ca2+ probes indo-1 and fura-2, in part in combination with electrophysiological tight seal whole cell recordings, obtained with the novel approach of patch perforation. It was demonstrated that adenosine receptor activation by N6-(R-phenyl-isopropyl)-adenosine (PIA) caused a block of electrical activity and abolished the ensuing alterations in [Ca2+]i. PIA mimicked the inhibitory action of somatostatin. Adenosine effects are mediated by A1 receptors in these cells and are antagonized by IBMX, an adenosine receptor blocker. PIA also suppressed action potentials that were elicited by the activation of protein kinase C with the phorbol ester PMA, or during the second phase of TRH action. In contrast, no interference was notable on TRH-induced intracellular Ca2+ mobilization. In addition to the abolition of Ca2+ transients, PIA lowers basal [Ca2+]i in some cells. It is proposed that in addition to the inhibition of adenylate cyclase, A1 receptor action on [Ca2+]i is an important element in the control of excitable pituitary cells.
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PMID:Adenosine A1 receptor-induced inhibition of Ca2+ transients linked to action potentials in clonal pituitary cells. 168 Jul 18

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.
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PMID:Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli. 168 1


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