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)

Adult monkey sensorimotor cortex consists of several structurally and functionally distinct areas. The developmental sequence through which the characteristic architectonic features and the borders of these areas become resolved was examined in a series of fetal, postnatal and adult monkeys by using Nissl staining, cytochrome oxidase and acetylcholinesterase histochemistry, and immunocytochemistry for GABA and the neuropeptides somatostatin, neuropeptide Y, substance P and cholecystokinin. At the youngest fetal age examined (E110), the pre- and postcentral gyri possess six clearly delineated cellular layers; populations of GABA- and neuropeptide-immunoreactive cells can be identified, but their somatic sensory cortex at E110 lacks areal cytoarchitectonic parcellation. Despite the apparent homogeneity in the cytoarchitecture of the somatic sensory cortex, incipient areal borders are revealed by staining for cytochrome oxidase and acetylcholinesterase activity, and by staining immunocytochemically for several neuropeptides. The motor cortex at E110 differs from that in adults by the presence of a prominent layer IV; a clear cytoarchitectonic border between areas 3a and 4 is detectable at E110, which is also revealed by chemoarchitectonic markers. With increasing age, the characteristic architectonic features gradually emerge and areal cytoarchitectonic borders appear, becoming adult-like by early postnatal ages. The gradual changes in cytoarchitecture are paralleled by redistributions of GABA- and neuropeptide-immunoreactive cells and fiber plexuses. The data demonstrate that the progressive refinement in cytoarchitectonic features and in the distributions of neurotransmitter- and peptide-containing cells occurs primarily during the latter third of gestation. The major changes are temporally coincident with the ingrowth of afferent axonal systems, suggesting that the establishment of connectivity may be capable of modulating finer details of structural or molecular phenotype, particularly intra-areal cytoarchitectonic features and neurotransmitter or peptide expression.
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PMID:The emergence of architectonic field structure and areal borders in developing monkey sensorimotor cortex. 171 47

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.
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PMID:Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease. 180 75

Different regions of the prostate gland, namely the prostatic capsule, peripheral prostate, and proximal and distal central prostate, were obtained from 5 patients with carcinoma of the bladder and studied histochemically and immunohistochemically to localise acetylcholinesterase (AChE)-, dopamine beta-hydroxylase (DBH)-, serotonin- and peptide-containing nerves. Autonomic ganglia were found in all regions of the prostate studied. The greatest number of ganglia contained AChE and neuropeptide Y (NPY) followed (in decreasing order) by DBH; [Met]enkephalin (mENK) and [Leu]enkephalin (IENK); calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP); and serotonin, but not somatostatin. The greatest density of nerve fibres was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least in the peripheral prostate. The greatest number of nerve fibres contained ACh and NPY, followed in decreasing order by VIP and DBH; IENK, serotonin and CGRP; mENK; substance P and somatostatin. The functions of the neurotransmitter substances in the human prostate remain to be elucidated.
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PMID:The human prostate gland: a histochemical and immunohistochemical study of neuropeptides, serotonin, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves and ganglia. 187 92

Cholinergic pathways play an important role in the regulation of GH secretion. To assess their participation in GH feedback, we investigated the effect of pyridostigmine (an acetylcholinesterase inhibitor) on plasma GH responses to GH-releasing hormone (GHRH) plus TRH, insulin hypoglycemia, and arginine as well as on the inhibition of these responses by exogenous GH. The GH response to each stimulus was inhibited by an infusion of GH (0.55 micrograms/m2/min), started 4 h earlier. Pyridostigmine (120 mg, orally), administered 30 min before the stimulus, enhanced GH responses to GHRH and insulin during both saline and GH infusions. However, GH responses during combined administration of pyridostigmine and GH were less than those during pyridostigmine alone. GH responses to arginine, in contrast, were not affected by pyridostigmine in either the absence or presence of exogenous GH. TSH responses to TRH were unaltered by either GH or pyridostigmine. Pyridostigmine enhancement of GH responses to a maximally stimulatory dose of GHRH suggests that its effect is exerted by inhibition of somatostatin release. The lack of effect of pyridostigmine on plasma GH responses to arginine suggests that arginine and pyridostigmine increase GH secretion through a common pathway. The enhancement by pyridostigmine of GH responses in both the presence and absence of exogenous GH suggests that exogenous GH and pyridostigmine exert their discordant effects on GH secretion through independent mechanisms.
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PMID:The role of the cholinergic pathway in growth hormone feedback. 190 84

The pattern of ischemia-induced cell death was examined with histochemical methods in the striatum of adult gerbils 4 and 7 days after transient forebrain ischemia. The results showed a massive loss of immunoreactivity to enkephalin and tachykinins, peptides present in striatal efferent neurons. In contrast, neurons expressing acetylcholinesterase activity, or choline acetyltransferase immunoreactivity, as well as neurons immunoreactive for somatostatin, were relatively preserved in areas of severe neuronal loss. The selective vulnerability of subpopulations of striatal neurons to transient ischemia in the adult is similar to that observed in the neonate and after local injections of agonists of N-methyl-D-aspartate receptors, but not of agonists of other glutamate receptor subtypes. It also presents striking similarities to the pattern of neuronal death observed in Huntington's disease. The results further support a role for overstimulation of a subtype of excitatory amino acid receptor in ischemia-induced cell death and show that the selective sparing of subpopulations of striatal interneurons after ischemic injury is not related to immaturity of these neurons but also occurs in the adult.
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PMID:Ischemic damage in the striatum of adult gerbils: relative sparing of somatostatinergic and cholinergic interneurons contrasts with loss of efferent neurons. 197 9

The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.
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PMID:Microtopography of D1 dopaminergic binding sites in the human substantia nigra: an autoradiographic study. 198 69

An impairment of cholinergic and somatostatinergic neurotransmission have been reported in dementia. Both acetylcholine and somatostatin are involved in the regulation of growth hormone (GH) secretion. The effects of GH-releasing hormone (GHRH) 1-44 on GH release have been studied before and after the pretreatment with pyridostigmine or pirenzepine in subjects with senile dementia of the Alzheimer type, multi-infarct dementia and mixed dementia. The data have been compared with those obtained in an age-matched healthy control group. The GH response to GHRH is similar in the patients and in the controls, though the peak occurrence is significantly delayed in dementia. The cholinesterase inhibitor pyridostigmine enhances significantly the GH response to GHRH in both groups. The responses obtained in demented subjects are significantly larger than those found in the controls. Pirenzepine, a muscarinic receptor blocker, inhibits the GHRH effect on GH secretion in both groups. The findings may be interpreted in terms of an underlying impairment of the hypothalamic cholinergic neurotransmission, with an acetylcholine receptor supersensitivity that becomes apparent when the cholinergic tonus is enhanced by the inhibition of cholinesterase by pyridostigmine. No significant differences, due to the type of dementia, have been observed.
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PMID:Cholinergic modulation of growth hormone-releasing hormone effects on growth hormone secretion in dementia. 198 29

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.
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PMID:Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children. 199 16

Growth hormone-releasing hormone (GHRH) increases serum GH levels in a dose-dependent manner. 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 if an enhancement of the cholinergic tone was able to influence the dose-response relationship between GHRH and GH in normal adult subjects. Six healthy adult volunteers underwent 10 experimental protocols. They were: human GHRH (1-29)NH2, 1 micrograms/kg injected as an intravenous (IV) bolus 60 minutes after (a) PD, 120 mg administered orally, or (b) placebo, two tablets administered orally; GHRH, 0.3 micrograms/kg injected as an IV bolus 60 minutes after (c) PD or (d) placebo; GHRH, 0.1 micrograms/kg injected as an IV bolus 60 minutes after (e) PD or (f) placebo; GHRH, 0.01 micrograms/kg injected as an IV bolus 60 minutes after (g) PD or (h) placebo; saline, 1 mL injected as an IV bolus 60 minutes after (i) PD or (l) placebo. The GH response in placebo-treated subjects was similar after 1 microgram/kg and 0.3 microgram/kg GHRH, while the 0.1 microgram/kg dose elicited a lower response. The 0.01 microgram/kg dose of GHRH did not significantly increase GH levels as compared with saline. After PD, the GH responses to GHRH were greatly enhanced at all doses tested: 1.0, 0.3, and 0.1 microgram/kg GHRH all elicited similar GH responses; the GH response to 0.01 microgram/kg GHRH was lower, but was still higher than that observed after saline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man. 202 38

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.
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PMID:Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children. 206 Jan 50


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