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)

A 40-yr-old man who had acromegaly and hyperthyroidism due to a GH/TSH-secreting pituitary adenoma is described. Serum free T4 was 2.8 ng/dl, free T3 was 1.1 ng/dl, and TSH was 1.2-1.5 microU/ml; the latter was measured in an immunoradiometric assay with a sensitivity of 0.07 microU/ml. Serum TSH was immunologically identical to standard TSH and did not decrease during a T3 suppression test. Serum free alpha-subunit and the molar alpha-subunit to TSH ratio were high (6.1 ng/ml and 31.2, respectively). TRH administration induced significant increases in both GH (+129%) and alpha-subunit (+156%) levels. Conversely, dopamine infusion resulted in a decrease in serum GH (-66%) and alpha-subunit (-43%) levels, and subsequent administration of the dopamine antagonist sulpiride induced significant increases in both GH and alpha-subunit (+393% and +106%, respectively). Similarly, somatostatin infusion inhibited GH (-43%) and alpha-subunit (-61%) secretion. Serum TSH levels were not affected by TRH, dopamine, or somatostatin. The biological to immunological activity ratio of serum TSH purified by immunoaffinity chromatography and measured in an adenylate cyclase assay was significantly increased compared to that in serum from hypothyroid or euthyroid subjects [biological to immunological activity ratio, 6.9 +/- 0.2 (+/- SD) vs. 4.4 +/- 1.1; P less than 0.001]. In gel chromatography, the apparent mol wt of the patient's TSH was smaller than that of the controls. After adenomectomy, all of the altered parameters of pituitary function became normal. Double gold particle immunostaining of the adenomatous tissue showed that all of the cells contained secretory granules positive for GH and alpha-subunit, while very few cells were positive for TSH beta as well as GH and alpha-subunit. These data indicate that in this patient serum TSH had an apparent mol wt smaller than that of normal TSH and an increased biological activity which, along with the autonomous TSH secretion, account for hyperthyroidism in the presence of low normal TSH levels; alpha-subunit originated from the same adenomatous cells that secreted GH but not TSH, thus explaining the in vivo observation that alpha-subunit responses to several agents were dissociated from TSH responses and parallel to GH responses; and TSH and GH were colocalized in a minority of the neoplastic cells.
 ...
PMID:Endocrine, biochemical, and morphological studies of a pituitary adenoma secreting growth hormone, thyrotropin (TSH), and alpha-subunit: evidence for secretion of TSH with increased bioactivity. 241 56

The cleavage of arachidonate from pituitary phospholipids may contribute to the process that regulates the release of prolactin. To test this hypothesis, primary cultures of anterior pituitary cells from female rats were preincubated with [3H]arachidonate to label their phospholipid-containing components. The cells were then washed and incubated with vehicle or test agents and the release into the medium of prolactin and [3H]arachidonate cleaved from the phospholipids was measured. Thyrotropin-releasing hormone (TRH) and neurotensin significantly increased the release of both [3H]arachidonate and prolactin. Although basal [3H]arachidonate release was not affected by dopamine or somatostatin, both of these agents reduced [3H]arachidonate release induced by TRH. The relationship between calcium mobilization and arachidonate release was investigated by exposing the cells to agents that modify calcium balance. Maitotoxin, a calcium channel activator, stimulated prolactin and arachidonate release. In contrast cobalt, a calcium channel blocker, penfluridol, a calcium-binding protein inhibitor, and low-calcium medium decreased basal and TRH-induced prolactin release and diminished the TRH-induced release of arachidonate. RHC 80267, an inhibitor of diacylglycerol lipase, decreased TRH-induced prolactin and arachidonate release. BW755c, an inhibitor of the conversion of arachidonate to its metabolites, decreased TRH-induced prolactin release but predictably increased arachidonate release. These findings support the hypothesis that arachidonate metabolites may be involved in the process regulating prolactin release.
 ...
PMID:A possible role of arachidonate metabolism in the mechanism of prolactin release. 242 Feb 3

The basis for understanding clinical disorders in the neuroregulation of GH secretion is derived from the complexity of the CNS-hypothalamic-pituitary axis. Studies in animals and humans demonstrate an anatomic, physiological and pharmacological evidence for neurosecretory control over GH secretion including neurohormones (GRH, somatostatin), neurotransmitters (dopaminergic, adrenergic, cholinergic, serotonergic, histaminergic, GABAergic), and neuropeptides (gut hormones, opioids, CRH, TRH, etc). The observation of a defect in the neuroregulatory control of GH secretion in CNS-irradiated humans and animals led to the hypothesis of a disorder in neurosecretion, GHND, as a cause for short stature. We speculate that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.
 ...
PMID:Growth hormone neurosecretory dysfunction. 242 94

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.
 ...
PMID:Raised thyrotrophin-releasing hormone, pyroglutamylamino peptidase, and proline endopeptidase are present in the spinal cord of wobbler mice but not in human motor neurone disease. 244 4

CSF samples from ten healthy volunteers and 22 patients with major depression were collected by lumbar puncture at 9 a.m. and the content of monoamine metabolites, corticotropin releasing factor (CRF) and somatostatin (SRIF) was analyzed. Plasma concentrations of TSH following a TRH challenge test (200 micrograms) and plasma cortisol following dexamethasone (1 mg; DST) were also analyzed. No relationships were observed between the CRF or SRIF concentrations and either basal or post-dexamethasone cortisol concentrations. Fourteen of 21 depressed patients were DST nonsuppressors using a plasma cortisol concentration cut off point greater than or equal to 138 nmol/l. If a more conservative cut off point was used (greater than 290 nmol/l) seven out of 21 patients revealed a severity-related cortisol nonsuppression. No significant difference was observed between healthy volunteers and depressed patients with regard to TSH response to TRH. The CSF content of CRF was elevated and the content of SRIF reduced in the depressed patients. In the healthy volunteers an inverse relationship was observed between CSF concentrations of CRF and MHPG (r = -0.72; P = 0.019); no relationship was observed between the concentrations of CRF and 5-HIAA or HVA. In the depressed patients positive correlations were found between CSF concentrations of CRF and 5-HIAA (r = 0.59; P = 0.004) and between CRF and HVA (r = 0.44; P = 0.042). These data are concordant with the view that norepinephrine and serotonin may be involved in the regulation of CRF secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Monoamine metabolites, corticotropin releasing factor and somatostatin as CSF markers in depressed patients. 245 42

The present study examines the effects of intrathecal administration of selected peptides on nociceptive responses in the rat. Each peptide was delivered via a chronically implanted catheter to the L5 vertebral level. In the tail flick test, VIP (0.65-6.5 nmoles) produced a dose-dependent decrease in reaction time (RT) from 1 to 6-16 min after injection; 6.5 nmoles decreased RT to 37% of control value at 1 min after injection. Galanin (0.65-6.5 nmoles) produced a dose-dependent increase in reaction time at 1 and 6 min; at high doses, many of the rats failed to flick the tail. CGRP (6.5 nmoles) produced a small, transient decrease in RT to 73% of control values at 1 min; 3.25 nmoles were without effect. CSF and 6.5 nmoles of somatostatin, TRH and angiotensin II were without effect. At high doses of galanin and CGRP, rats vocalized to innocuous touch of the tail, as reported for substance P. Von Frey hairs were thus applied to the tail after 6.5 nmoles of VIP, galanin, CGRP or substance P. Vocalization in response to a previously innocuous pressure stimulus was observed at 30 s after injection in all rats given galanin and some rats given CGRP or substance P; the effect lasted 4-8 min. VIP and CSF had no effect. These results suggest that VIP, galanin, CGRP and substance P may act as excitatory agents in nociceptive pathways and that specific peptides may function in the different types of pain modalities; VIP in thermal, galanin in mechanical and substance P and CGRP in both.
 ...
PMID:Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. 245 92

The septo-hippocampal neurons (SHNs), located in the medial septum, project to the hippocampal formation. The population of SHNs, as shown by single unit recordings in urethane-anesthetized rats, is heterogeneous, both in terms of patterns of spontaneous activity (a significant proportion of the SHNs display a characteristic rhythmically bursting activity at about 4 Hz) and of conduction velocity. Their average rate of spontaneous discharge is quite high (20 impulses per second). They are excited by the iontophoretic application of acetylcholine and various cholinergic agonists. They are also excited by some peptides such as substance P and TRH. Parallel studies in aged animals show that the physiological properties of the SHNs are altered, while their pharmacological properties seem to be unchanged. Immunohistochemical investigations using antibodies against various peptides and a monoclonal antibody against choline acetyltransferase (ChAT) show that SHNs retrogradely-labeled from the hippocampus often contain ChAT, less frequently galanin-like immunoreactivity and in a few cases enkephalin, luteinizing hormone-releasing hormone, or calcitonin gene-related peptide. In contrast, cholecystokinin, vasoactive intestinal peptide, substance P, somatostatin, dynorphin-B and neurotensin, although present in some medial septal neurons, were never observed in neurons projecting to the hippocampus.
 ...
PMID:Neuropeptides and septo-hippocampal neurons: electrophysiological effects and distributions of immunoreactivity. 247 66

Neuropeptides such as vasoactive intestinal peptide, LHRH, or TRH have been found in rat pituitary tissue and could act via paracrine or autocrine actions in this tissue. In this study we investigated whether normal human pituitary tissue and GH-secreting human pituitary adenomas could release somatostatin (SRIH) and GHRH. Fragments from three human pituitaries and dispersed cells from six GH-secreting adenomas (four adenomas were studied for GHRH release and five for SRIH release) were perifused using a Krebs-Ringer culture medium, and the perifusion medium was collected every 2 min (1 mL/fraction for 5 h). GH, GHRH, and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L TRH or SRIH. Both normal pituitaries and GH-secreting pituitary adenomas released SRIH and GHRH. SRIH release commenced 90-180 min after initiation of the perifusion, at which time GH secretion had decreased significantly. TRH stimulated SRIH release from normal pituitary tissue and inhibited SRIH release from adenoma tissue. GHRH was present at the start of the perifusion, but rapidly disappeared. However, SRIH stimulated GHRH release from normal pituitary tissue, but not from adenoma tissue. Significant amounts of GHRH and SRIH were released during the experiments, suggesting their local synthesis. These results indicate that pituitary cells can release hypothalamic peptides. The liberation of these neuropeptides is regulated, and moreover, their regulation differs between normal and adenomatous pituitaries.
 ...
PMID:Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone. 249 37

We used the reverse hemolytic plaque assay to study the dynamics of GH secretion by individual pituitary adenoma cells from eight acromegalic patients. There was a considerable variation between the adenomas with respect to the percentages of GH-secreting cells (25-78.5%) and also with respect to the amount of GH released per individual pituitary adenoma cell (mean plaque areas varying from 901-3559 micron 2). The GH plaque area frequency distributions from the adenoma cells were not normally distributed, but revealed a preponderance of small plaques, defined as those with areas smaller than the mean plaque area. The large plaques, that is those with areas larger than the mean plaque area, constituted 24-38% of the total cell population from different tumors and accounted for a large fraction (63-80%) of the total plaque area (the total amount of GH released by the adenoma cells). The somatostatin analog SMS 201-995 caused a shift in the GH plaque area frequency distributions toward smaller plaques, but had no effect on the overall percentages of GH plaque-forming cells in three of the five adenomas in which it was studied. This finding suggests that the adenoma cells from these patients that formed large plaques were preferentially inhibited by SMS 201-995. GHRH (studied in two adenomas) and TRH (studied in one adenoma) had no preferential effect on any subpopulation of adenoma cells. We conclude that GH secretion by individual somatotroph adenoma cells is highly variable both within and between adenomas and that SMS 201-995 has a preferential inhibitory effect on a subpopulation of adenoma cells in some adenomas.
 ...
PMID:Heterogeneity of growth hormone (GH) release by individual pituitary adenoma cells from acromegalic patients, as determined by the reverse hemolytic plaque assay: effects of SMS 201-995, GH-releasing hormone and thyrotropin-releasing hormone. 249 40

The pattern of TSH secretion in man in pulsatile in addition to the well known circadian variation. The mechanism triggering TSH pulses remains unclear to date. Infusions of somatostatin or dopamine rapidly lowering basal TSH levels without suppressing the pulsatile pattern suggest that an episodic disinhibition exerted by a physiological inhibitor is not a likely cause. On the same basis, thyroid hormones do not appear to be candidates, since they similarly inhibit basal TSH levels after a time lag of several hours but again do not suppress pulsatile release of the hormone. In contrast, bolus injections of dexamethasone completely abolish pulsatile release of TSH for several hours despite a normal sensitivity of the pituitary to exogenous TRH, suggesting a hypothalamic action of the drug. The hypothesis that pulsatile TSH release might be governed by a pulsatile mode of a hypothalamic stimulator is supported by the observation that an infusion of nifedipine, a calcium channel blocker, which in vitro selectively inhibits the TRH effect on TSH but not prolactin secretion, exerts a comparable effect when it is infused in vivo.
 ...
PMID:Physiological regulation of thyrotropin. 249 28


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