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)

Several lines of evidence suggest that somatostatin (SS) may interact with serotonergic neurons in the central nervous system. To assess whether SS acts presynaptically on serotonin (5-hydroxytryptamine, (5-HT)) neurons, SS receptors were measured in membranes from the hippocampus, a brain region that receives dense serotonergic innervation and has a high number of SS receptors in control and 5,7-dihydroxytryptamine (5,7-DHT)-treated rats, at 1 and 3 weeks after injection. Intracerebroventricular (i.c.v.) injection of the 5-HT-specific neurotoxin 5,7-DHT (11 micrograms (free base) dissolved in 10 microliters of isotonic saline containing 0.01% ascorbic acid) produced a 70% reduction in hippocampal 5-HT content at 3 weeks after injection but not at 1 week. This change was associated with a significant decrease in SS receptor density in rat hippocampus only at 3 weeks following the injection, without influencing the apparent affinity of the receptors at any time. Administration of 5,7-DHT did not affect somatostatin-like immunoreactivity (SSLI) levels at both times studied. These results suggest that some of the hippocampal SS receptors may be localized presynaptically on the serotonergic nerve terminals.
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PMID:Reduction of somatostatin receptors in rat hippocampus by treatment with 5,7-dihydroxytryptamine. 136 78

Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.
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PMID:Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat. 168 89

The aim of the present study was to evaluate the physiological role of intrapancreatic serotonergic nerves for endocrine pancreatic function. The specific uptake of [3H]5-hydroxytryptamine (5-HT) into pancreatic slices from the rat was completely abolished after an intrapancreatic injection of 5,7-dihydroxytryptamine (5,7-DHT). Since also high-affinity uptake of [3H]5-HT was absent it was concluded that intrapancreatic serotonergic nerves were destroyed. The effects of this selective denervation on glucose-stimulated insulin and somatostatin secretion were investigated with the aid of perfused rat pancreatic glands removed 3, 7 or 14 days after the injection of 5,7-DHT. Neither the basal release of these hormones nor their response to a glucose challenge was significantly altered by the ablation of the intrapancreatic serotonergic nerves. The microsphere technique was used to investigate the blood flow through the pancreatic islets in rats injected intrapencreatically with 5,7-DHT 4 days previously. No significant changes in either the whole pancreatic blood flow or the islet blood flow could be demonstrated. These result show that in normal physiological conditions the intrapancreatic serotonergic nerves do not affect the hormonal release from or the blood flow through the endocrine pancreas.
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PMID:Ablation of serotonergic nerves in the rat pancreas. Lack of effects on hormone secretion and intrinsic blood flow. 286 99

To date, it is unknown whether intrapancreatic serotonergic nerves can influence pancreatic somatostatin (SS) content and the SS receptor/effector system in the exocrine pancreas. In this study, the intrapancreatic serotonergic nerves were chemically ablated by injecting a specific serotonin (5-HT) neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the substance of the gland. Three days after the injection, the 5-HT-like immunoreactive levels in the pancreas were reduced by more than 85% whereas somatostatin-like immunoreactive levels had increased (86%). The number of SS receptors in the pancreatic acinar cell membranes of the 5,7-DHT-treated rats was also increased (72%). No significant differences were seen in basal or forskolin-stimulated adenylate cyclase (AC) enzyme activities in the control and the 5,7-DHT-treated groups. In spite of the increase in the number of SS receptors in the pancreatic acinar cell membranes of 5,7-DHT-treated rats, SS caused a significantly lower inhibition of AC activity in these membranes. This finding is related to the observed decrease of a 41 kD pertussis toxin-sensitive substrate, presumably the alpha i subunit of the guanine nucleotide inhibitory protein, in pancreatic acinar cell membranes 3 days after intrapancreatic 5,7-DHT administration when compared with the corresponding controls. The functions of pancreatic serotonergic nerves seem to be associated with enteropancreatic communication. These data together with the present results suggest that pancreatic SS content and the SS receptor/effector system in the exocrine pancreas may be regulated by enteropancreatic serotonergic nerve fibers and may participate in enteropancreatic reflexes.
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PMID:Pancreatic changes in somatostatin content and receptor/effector system after intrapancreatic injection of 5,7-dihydroxytryptamine. 761 56

The levels of five neuropeptides (substance-P, somatostatin, cholecystokinin octapeptide, methionine-enkephalin and dynorphin) were examined in the brain and the spinal cord of rats 2 weeks after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT). 5,7-DHT injection caused a significant reduction of the serotonin level in all regions of the brain. The level of each neuropeptide except dynorphin significantly increased in specific regions of the brain after 5,7-DHT treatment without any decrease in their levels in any region. Since, coexistence and interaction between classical neurotransmitters and neuropeptides in the same neurons have been reported, both are indispensable for evaluating pathophysiological state of the brain function associated with abnormal neural transmission. The present findings together with previous reports suggest that neuropeptides act as neurotransmitters and compensate for the impaired function of the serotonergic systems.
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PMID:Regional changes in neuropeptide levels after 5,7-dihydroxytryptamine-induced serotonin depletion in the rat brain. 769 Feb 30

The levels of neuropeptide Y and somatostatin may change when serotoninergic neurotransmission is altered in different brain regions. To assess whether serotonin regulates the synthesis of these peptides, we measured the levels of preproneuropeptide Y (ppNPY) and preprosomatostatin (ppSOM) mRNA in different brain regions after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), a selective serotonin neurotoxin. The mRNA of these peptides significantly increased in the striatum but not in hippocampus and frontal cortex. It thus appears that serotonin has an inhibitory effect on the biosynthesis of neuropeptide Y and somatostatin in striatum whereas it probably acts by stimulating the release of these peptides in hippocampus and frontal cortex.
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PMID:Increased expression of preproneuropeptide Y and preprosomatostatin mRNA in striatum after selective serotoninergic lesions in rats. 790 49

In order to investigate the possibility that, in the rat, some cerebral cortex somatostatin (SS) receptors may be localized presynaptically on the terminals of serotonergic neurons, serotonin [5-hydroxytryptamine, (5-HT)] neurons in the central nervous system were damaged with a local intracerebral injection of the serotonergic neurotoxin, 5,7-dihydroxytryptamine(5,7-DHT). The injection of 5,7-DHT (11 micrograms free base dissolved in 10 microliters of isotonic saline containing 0.01% ascorbic acid) in rats produced an reduction by about 74% in frontoparietal cortical 5-HT content at 1 and 3 weeks after injection. These changes were associated with a significant decrease by about 30% in the total number of specific SS receptors in the frontoparietal cortex at both times studied without influencing the apparent affinity of the receptors. Together, these results suggest that a portion of the frontoparietal cortex SS receptors may be localized presynaptically on the serotonergic nerve terminals. The 5,7-DHT did not affect SS-like immunoreactivity (SSLI) levels suggesting that SS and 5-HT are not colocalized within the same neuronal elements in the rat frontoparietal cortex.
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PMID:Effect of serotonin axon injury on the somatostatinergic system in rat frontoparietal cortex. 843 9

Pituitary transcription factor-1 (Pit-1 or GHF-1) is a transcription factor specific to the anterior pituitary and is involved in the expression and regulation of the growth hormone (GH), prolactin (PRL) and thyroid-stimulating hormone (TSH) beta-subunit genes. The expression of these three genes can be modulated by changes in the hormone environment and it is thought that some of these effects are mediated through Pit-1, but little is known about the physiological regulation of this transcription factor. Therefore, we first asked whether Pit-1 gene expression is modified as a result of changes in the in vivo gonadal steroid environment and if this could be correlated with changes in GH and/or PRL mRNA levels. Secondly, we sought to determine if sex steroids affect the mRNA levels of these three peptides by acting at the level of the pituitary and whether these effects are androgen or estrogen mediated. Finally, how sex steroids modulate the response of these three genes to the hypothalamic neuropeptides growth hormone-releasing hormone (GHRH) and somatostatin (SS) was analyzed. To this end, we compared Pit-1, GH and PRL mRNA levels in the anterior pituitary of intact, castrated, and castrated testosterone-replaced adult male rats. In addition, primary cultures of adult male pituitaries were used to study the direct effects of both androgens and estrogens on Pit-1, GH, and PRL mRNA levels. In situ hybridization histochemistry was used to compare relative levels of Pit-1, GH and PRL mRNA. Densitometric analysis of the in vivo studies showed that castration resulted in a 57, 40 and 55% decline in Pit-1, GH and PRL mRNA signal levels, respectively. Furthermore, replacement with testosterone (T) at the time of castration completely prevented the decline in all three mRNA species (ANOVA: Pit-1 mRNA, p < 0.0001; GH mRNA, p < 0.0001; PRL mRNA, p < 0.0001). In vivo, both T (10(-7) M) and estradiol (10(-9) M) were capable of stimulating Pit-1 mRNA and PRL mRNA levels, while dihydrotestosterone (DHT; 10(-7) M) had no effect. There was no effect of any of these steroid treatments on GH mRNA levels in vitro. Addition of GHRH to the cultures increased GH mRNA levels, as well as those of Pit-1 and PRL, and SS had the opposite effect on GH mRNA levels. Whereas the GH response to GHRH was not significantly modified by exposure to sex steroids, the effect of SS was. The presence of sex steroids was capable of modifying the Pit-1 and PRL responses to both GHRH and SS. These results clearly indicate that changes in circulating levels of sex steroids modulate the expression of Pit-1 in the anterior pituitary and that these changes can be correlated with commensurate modifications in GH and PRL mRNA levels. Furthermore, the effect on both Pit-1 and PRL mRNA levels occurs, at least in part, at the level of the anterior pituitary and is an estrogen-receptor-mediated event. In contrast, the effects of gonadal steroids on GH mRNA levels are less direct and are most likely mediated at the level of the hypothalamus, as well as through modulation of the response of the somatotroph to hypothalamic factors. We conclude that the transcription factor Pit-1 is actively regulated physiologically and may be involved in mediating some of the effects of sex steroids and hypothalamic factors on the synthesis of certain anterior pituitary hormones.
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PMID:In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment. 883 50

Anterior pituitary hormone secretion is sexually dimorphic due partially to gender differences in the postpubertal hormone environment; however, differences in the pituitary's responsiveness to these signals may also play a role. We have used simple and double in situ hybridization to determine whether lactotrophs and somatotrophs from male and female rats respond differently in vitro to growth hormone-releasing hormone (GHRH), somatostatin (SS) or insulin-like growth factor (IGF)-I and whether sex steroids modulate these responses. Cultures were treated with either 17 beta-estradiol (E; 10(-9)M), testosterone (T; 10(-7)M), dihydrotestosterone (DHT; 10(-7) M) or vehicle in combination with either GHRH (10(-7)M), SS (10(-7)M), IGF-I (10(-7)M) or vehicle. Basal mRNA levels of GH, prolactin (PRL) and pituitary transcription factor-1 (Pit-1) did not differ between the sexes. The responses to peptide hormones alone were similar between the sexes, but not in the presence of gonadal steroids. In females, DHT reduced and E increased the stimulatory effect of GHRH and inhibitory effect of SS on GH mRNA levels (two-way ANOVA: P < 0.05), while having no effect in males. An additive effect of E and GHRH on PRL mRNA levels was seen only in males. The E induced rise in PRL mRNA levels was completely inhibited by SS in females, but only partially so in males (two-way ANOVA: P < 0.001). IGF-I inhibited the E induced rise in PRL and lactotroph Pit-1 mRNA levels only in females. These results suggest that sex steroids modulate the pituitary's response to hypothalamic and circulating factors differently in males and females and that this may play a role in generating the sexually dimorphic patterns of pituitary hormone secretion.
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PMID:Sexually dimorphic interaction of insulin-like growth factor (IGF)-I and sex steroids in lactotrophs. 970 Jun 76

Our recent work showed that the brain serotonergic system negatively regulated liver cytochrome P450. The aim of our present research was to study the effect of damage to the serotonergic innervation of the paraventricular (PVN) or arcuate nuclei (ARC) of the hypothalamus on the neuroendocrine regulation of cytochrome P450 (CYP). Male rats received bilateral injections of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the PVN or ARC. One week after the injection brain neurotransmitters, serum hormones (growth hormone, testosterone, corticosterone, thyroid hormones), pituitary somatostatin and liver cytochrome P450 expression and activity were measured. Lesion of the serotonergic innervation of the PVN decreased serotonin level in the hypothalamic area containing the PVN, causing an increase in growth hormone and testosterone concentrations in the blood and, subsequently, an increase in the expression (mRNA and protein level) and activity of isoform CYP2C11 in the liver. In contrast, damage to the serotonergic innervation of the ARC, which caused a decrease in serotonin level in the hypothalamic area containing the ARC, reduced the concentration of growth hormone and the expression and activity of CYP2C11. In conclusion, the obtained results show a reverse effect of the serotonergic innervation of the hypothalamic paraventricular (a negative effect) and arcuate nuclei (a positive effect) on growth hormone secretion and growth hormone-dependent CYP2C11 expression. They also suggest that CYP2C11 expression may be changed by drugs acting via the serotonergic system, their effect depending on their mechanism of action, route of administration (intracerebral, peripheral) and distribution pattern within the hypothalamus.
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PMID:The reverse role of the hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei in the central serotonergic regulation of the liver cytochrome P450 isoform CYP2C11. 2713 92


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