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)

Dairy cows in early lactation were reported to secrete growth hormone in response to declining glucose concentrations at day 5 but not day 30 post-partum, whereas GH responses to TRH were reported to be enhanced after day 30 post partum. The present study examined GH response following glucose infusion and the effect of GHRH as well as effects of SRIH on GHRH-stimulated GH release. Declining plasma glucose concentrations after glucose infusion stimulated GH release at day 5 post partum but not in nonpregnant, nonlactating cows or in cows at days 30 and 90 post partum. GHRH stimulated GH release on all days tested, but the response was highest at day 30 post partum when compared to other days. Somatostatin infusion inhibited GHRH effects on GH concentrations only at day 30 post partum and in nonpregnant, nonlactating cows. Thus, a differential response of the GH regulatory system could be demonstrated between days 5 and 30 post partum utilizing different stimuli. Evaluation of plasma glucose and free fatty acid concentrations on days 5, 10, 20, and 30 post partum revealed a progressive decrease in FFA but not glucose as lactation progressed. Decreased plasma FFA concentrations were paralleled by a decrease in basal GH, somatomedin-C and epinephrine. Thus, a decline in FFA may be responsible for the disparity between effects of GHRH and glucose on GH release between days 5 and 30 post partum.
 ...
PMID:Differential growth hormone responses to glucose and growth hormone releasing hormone in lactating dairy cows. 256 12

Mice were given 10 micrograms somatostatin or 25 micrograms TRH intraperitoneally 10 min before s.c. injection of 2 or 20 mg CCl4. The extent of liver cell necrosis and nuclear size were measured by the electronic Mini Mop method and the extent of necrosis and nuclear pleomorphism were estimated by a visual linear analogue scale of 100 mm, and compared to plasma concentrations of ASAT and ALAT. Pre-treatment with TRH or somatostatin resulted in significant reduction in the extent of necrosis 24 h after CCl4-injections (25%), with a lowering of ASAT from 13209 +/- 2955 U/l to 5144 +/- 924 after TRH and to 6186 +/- 966 after somatostatin, and of ALAT from 14343 +/- 3209 to 7718 +/- 1727 and 6494 +/- 1253 U/l, respectively. After 3 days the necroses were reduced from 16.5 +/- 1.7% by the Minimop method to 1.4 +/- 0.5% (90%) in mice given CCl4 alone, and from 12.3 +/- 1.7% to 3.8 +/- 1.2% in mice pretreated with TRH, and from 12.3 +/- 1.8% to 3.8 +/- 1.7% (70%) in mice pretreated with somatostatin. The plasma concentrations of ASAT and ALAT were reduced correspondingly. After 5 days no necroses were seen, and the plasma ASAT and ALAT were normal. After 6 months of weekly injections of TRH or somatostatin before 20 mg CCl4 the liver cell nuclear size (10.5 and 9.7 0.3 mu 2) was similar to that after CCl4 alone (9.7 0.3 mu 2), and twice that of controls (4.6-5.4 0.1 mu 2). Liver cell necrosis was not seen. The plasma concentrations of ASAT (131 8.6-162 11.3) and ALAT (98 8-104 9 Iu/l) were similarly 2-3 times those in controls. TRH and somatostatin thus reduced liver cell injury and delayed regeneration after single injections of CCl4. After 6 months of weekly injections no effects were observed.
 ...
PMID:Liver cell necrosis and regeneration following injections of carbon tetrachloride. Effects of the thyrotropin-releasing hormone and somatostatin. 256 17

In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.
 ...
PMID:Receptors and neurohormones in human pituitary adenomas. 256 72

To determine whether GH feedback affects both induced and spontaneous GH secretion and to explore its neurotransmitter mediation, we assessed the effects of 6-h GH infusions (0.55-5.5 micrograms/m2/min) on sleep-associated and GH-releasing hormone (GHRH)-, insulin hypoglycemia-, and arginine-stimulated GH secretion and their modulation by beta-adrenergic blockade in normal men. GH infusions initiated 2 h before the expected onset of sleep produced a dose-dependent inhibition of GH secretion. GH infusions (0.55 micrograms/m2/min) initiated 4 h before the stimuli inhibited the GH response to each, but did not alter the TSH response to TRH. Propranolol infusion (80 micrograms/min) started 2 h before the onset of sleep or the stimulus enhanced GH responses to GHRH and insulin alone and in the presence of GH. In contrast, propranolol neither enhanced the GH responses to arginine or sleep nor reversed the inhibitory effects of GH. The negative feedback effect of GH to both physiological and pharmacological stimuli of GH secretion indicates that it is most likely mediated by both stimulation of somatostatin and inhibition of GHRH release. The effects of beta-adrenergic blockade suggest an inhibition of somatostatin release, although the complex interaction of GH and propranolol implies that they act through dissimilar mechanisms.
 ...
PMID:Beta-adrenergic modulation of growth hormone (GH) autofeedback on sleep-associated and pharmacologically induced GH secretion. 257 14

Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids; mature SRIF is located at the carboxyl-terminus of the precursor. We have used a recombinant retroviral expression vector encoding anglerfish prepor-SRIF-I to infect rat pituitary GH3 cells. The aim of these studies was to investigate the intracellular storage and secretion of the total pool of endogenous GH compared to that of SRIF. Several clonal lines of GH3 cells expressing high or low levels of SRIF were treated with TRH, forskolin, or depolarizing concentrations of potassium, and the levels of intracellular and secreted GH or SRIF were determined using highly sensitive RIAs. Approximately 65% of the total GH was secreted basally, whereas less than 20% of the SRIF-immunoreactive material was basally secreted. Forskolin treatment or potassium depolarization stimulated GH release, but only about 50% above basal levels. In contrast, SRIF secretion was stimulated approximately 5-fold in response to these secretagogues. Based on its lower basal rate of secretion compared to GH and its enhanced release in response to a variety of secretagogues, we conclude that the heterologously expressed SRIF is preferentially targeted to the regulated pathway in GH3 cells.
 ...
PMID:Retrovirus-mediated expression of preprosomatostatin in rat pituitary GH3 cells: targeting of somatostatin to the regulated secretory pathway. 257 12

In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.
 ...
PMID:Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. 257 6

The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 receptor analogues also inhibit TRH-stimulated [Ca2+]i-mobilization in GH3 cells. Both effects of the adenosine receptor agonists are apparently mediated by pertussis toxin substrates, of which there are two--41,000 and 40,000 daltons respectively--in these cells. Somatostatin exerts analogous effects to the adenosine agonists in GH3 cells. Thus it may turn out that a general property of 'cyclase inhibitory receptors' is also to inhibit [Ca2+]i-mobilization in the same cells, when such mechanisms are present.
 ...
PMID:Adenosine A1 receptors inhibit both adenylate cyclase activity and TRH-activated Ca2+ channels by a pertussis toxin-sensitive mechanism in GH3 cells. 257 20

It seems clear from the studies reviewed here that there is adequate evidence to support the concept of a biphasic response of the thyroid gland to cold as first postulated by Moll et al. (1972). The initial response to acute exposure to cold begins at the level of the hypothalamus as a result of either neural stimuli from skin and other areas and/or blood of somewhat lower than normal temperature reaching the hypothalamus (Andersson et al., 1963). As a result, the secretion of norepinephrine and/or dopamine may increase, and serotonin and/or somatostatin may decrease. The net result of these is an increase in the release of TRH from the hypothalamus. This, in turn, stimulates the cascade for the release of TSH from the anterior pituitary gland and thyroid hormone from the thyroid gland. Moll et al. (1972) postulated the lack of a feedback limb in this acute phase, and, indeed, this may be the case. It is possible, however, that certain hormones, such as somatostatin, norepinephrine, T3, and T4 could act in the capacity of feedback inhibitors. Additional experiments will be required to assess this possibility. The transitional link between the acute (less than 1 day) and chronic (greater than 1 day) phases of the response of the thyroid gland to cold could be T4 itself. An increase in the concentration of T4 in plasma has been reported to increase peripheral deiodination of T4 to T3 by kidneys and liver of rats. There are no studies at present to indicate that hepatic conjugation can be increased by elevation of plasma levels of T4 and T3. If it can, these responses would provide adequate reasons as to why peripheral metabolism of thyroid hormones increases during chronic exposure to cold. The time-course for these changes to occur needs to be studied in greater detail to establish the sequence of events following acute exposure to cold. The latter may also increase urinary excretion of T4 and T3 in man, but not the rat. This suggests that another aspect of exposure to cold needing additional study is measurement of the binding affinities of T4 and T3 for their transport proteins during exposure to cold as compared to affinities prior to exposure to cold. If binding affinities are reduced, the amount of free hormones would increase and, consequently the likelihood of being excreted into urine and conjugated by the liver would also increase.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Activity of the hypothalamic-pituitary-thyroid axis during exposure to cold. 265 59

Directional behavioral and functional asymmetries (i.e., left-biased or right-biased in all or most animals of the population) induced by certain chemical substances are new types of brain and spinal cord asymmetry. The revealed asymmetry comprises: (1) left- or right-biased circle rotation in rat, (2) hind limb postural asymmetry resulting from alteration of the left or right flexion reflex in rat and cat, and (3) asymmetric alterations of the evoked potentials (EP) in the turtle visual cortex. Circle rotation of animals is induced by hypothalamic neurohormones (somatostatin, LH-RH, substance P, and TRH). Postural asymmetry develops under the effect produced by enkephalins and opioid kappa- and delta-agonists, sigma-agonist SKF 10.047, Arg-vasopressin. Endogenous peptide factors, the activity (or content) of which increased under brain and spinal cord unilateral injury, as well as the ones localized in the left or right hemisphere, also induced postural asymmetry. EP of the left and right turtle visual cortex were inhibited by enkephalins and opioid kappa-, and delta- and mu-agonists, and factors predominantly localized in the left or right turtle visual cortex in a different manner. The data reported here suggest the existence of a side-specific mechanism for a selective neurohormonal regulation of the neuronal activity and other processes in the left and right halves of brain and spinal cord which involves lateralized neuropeptides and their receptors. This mechanism might serve to maintain a certain balance between the activity of the left and right-side neurons, and other contralateral processes in the paired and bilateral structures in brain and spinal cord. Significant deviations from the balance occur most likely due to powerful unilateral stimuli, e.g., unilateral trauma. Many neuropeptides (opioid ones, somatostatin, MSH, ACTH) are, presumably, involved in the regeneration processes in the central and peripheral nervous system. In the case of brain lesions, some lateralized endogenous peptides may participate in the regulation of regeneration process on the left, whereas the other ones, on the right side of the midline, which depends on the side of the lesion. Some lateralized receptors and ligands may serve as positional markers of the left, whereas the other ones may serve as those of the right brain hemisphere. In ontogenesis, these markers are probably necessary to perform the function of the mechanism responsible for symmetrical brain formation.
 ...
PMID:Neuropeptides induce directional asymmetry in brain and spinal cord: facts and hypotheses. 268 85

A 40-year-old woman, who had previously received radioactive iodine for hyperthyroidism, presumably due to Graves' disease, subsequently was found to have inappropriately elevated serum TSH and alpha-subunit levels and a pituitary adenoma. Detailed clinical studies revealed marked serum TSH elevations (approximately 100 mU/L) with no circadian variation, but with 7 pulses/24 h. Serum alpha-subunit levels averaged 2.5 micrograms/L, with 13 pulses/24 h. Neither serum TSH nor alpha-subunit responded to TRH stimulation, nor did serum TSH change during dopamine infusion, but alpha-subunit levels did decline slightly. In contrast, during somatostatin infusion, serum TSH declined to 30% of baseline levels, while alpha-subunit levels did not change. Pituitary adenoma tissue obtained at the time of transsphenoidal surgery immunostained weakly with anti-TSH beta serum and strongly with anti-alpha-subunit serum. Northern blot analysis of RNA isolated from the tumor revealed TSH beta and alpha-subunit mRNA levels of normal length, while primer extension analysis showed a major initiation site for the TSH beta gene that appeared to be identical in the tumor and normal pituitary tissue. A second minor upstream start site was detected in the tumor, but it represented less than 1% of transcription compared to the major downstream start site. We conclude that the tumor secreted TSH and alpha-subunit in an abnormal and discordant fashion, but that the TSH gene initiation site appeared to be normal and, therefore, did not explain the observed secretory abnormalities.
 ...
PMID:Clinical and molecular studies of a thyrotropin-secreting pituitary adenoma. 272 29


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