Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that administration of the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP), increases plasma concentrations of oxytocin, prolactin, corticosterone, induces penile erections and excessive grooming in male rats. To test the hypothesis that the hypothalamic paraventricular nucleus mediates these neuroendocrine and behavioural responses, we measured the effects of m-CPP (0.6 mg/kg i.v.) on these parameters in chronically cannulated, freely moving male rats after surgical lesion of the paraventricular nucleus or sham operation. Paraventricular nucleus lesion markedly attenuated prolactin, corticosterone and excessive grooming, but not oxytocin and penile erection responses to m-CPP. In contrast, both oxytocin and corticosterone responses to the dopamine receptor agonist, apomorphine (0.05 mg/kg i.v.), were attenuated in lesioned rats. The present studies suggest that the paraventricular nucleus mediates m-CPP-induced prolactin, corticosterone and probably also excessive grooming responses, and the mechanisms of apomorphine and m-CPP action on oxytocin secretion and penile erection responses differ.
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PMID:Paraventricular nucleus controls 5-HT2C receptor-mediated corticosterone and prolactin but not oxytocin and penile erection responses. 776 99

To test the hypothesis that the mechanisms of 5-HT1 and 5-HT2 receptor-mediated hormonal responses are different, we compared the effects of hypothalamic paraventricular nucleus (PVN) lesions on the ACTH/corticosterone, prolactin and oxytocin responses to the 5-HT1A agonist ipsapirone (1 and 2 mg/kg), the 5-HT2C agonist m-chlorophenylpiperazine (m-CPP, 0.6 mg/kg), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg) in chronically cannulated, freely moving male rats. Pharmacological characterization using antagonists with different affinity for 5-HT2A and 5-HT2C receptors revealed that DOI's responses were mediated mainly by 5-HT2A receptors and m-CPP's responses were almost exclusively mediated by 5-HT2C receptors. ACTH/corticosterone responses to ipsapirone, DOI and m-CPP were almost completely blocked after PVN lesions. Prolactin responses were significantly different in lesioned rats only after DOI and m-CPP challenges. Oxytocin responses to ipsapirone and DOI, but not m-CPP were markedly attenuated after PVN lesions. The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5-HT2A, or 5-HT2C receptors.
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PMID:Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses. 878 18

m-Chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT receptor function in human subjects, has been found to induce oxytocin and thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any effect on plasma oxytocin, TSH and aldosterone concentration in healthy volunteers using a double-blind, placebo-controlled crossover design. Plasma adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally accepted markers of m-CPP-induced 5-HT receptor activation, were measured in parallel. Male subjects (n=7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In female subjects (n=5), the effects of placebo and 0.25 mg/kg m-CPP were studied. After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH, cortisol and TSH concentrations; these responses were significant. At the dose of 0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone concentrations. Significant plasma oxytocin responses were found in female subjects only; thus this effect of m-CPP was statistically significantly gender dependent. Other responses to m-CPP were similar in male and female subjects. The present results suggest that there are clear differences, including dose and gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced neuroendocrine responses.
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PMID:Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m-chlorophenylpiperazine in healthy subjects. 960 May 79

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.
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PMID:Selective serotonin reuptake inhibitors and neuroendocrine function. 1050 38

The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2C receptor agonist (-)DOI [(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((+/-)-alpha(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (-)DOI in conscious rats. (-)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2C receptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (-)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (-)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (-)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.
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PMID:Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI. 1241 89

The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice.
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PMID:Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice. 1261 26

The neurotransmitter serotonin (5-HT) stimulates the secretion of vasopressin and oxytocin, and 5-HT is involved in the mediation of the vasopressin and oxytocin response to stress. In male Wistar rats, we investigated the 5-HT receptors involved in the 5-HT-induced increase of mRNA expression of vasopressin and oxytocin in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The 5-HT precursor, 5-hydroxytryptophan, injected in combination with the 5-HT reuptake inhibitor, fluoxetine, increased oxytocin mRNA expression in the PVN, and the concentration of vasopressin and oxytocin in plasma, whereas mRNA in the SON was not affected. Intracerebroventricular infusion of 5-HT agonists selective for the 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptor increased oxytocin mRNA in the SON and PVN. Infusion of agonists selective for the 5-HT2A + 2C receptor increased vasopressin mRNA in the PVN, whereas none of the 5-HT agonists affected vasopressin mRNA in the SON. All the 5-HT agonists infused increased peripheral oxytocin concentration and vasopressin was increased by stimulation of the 5-HT2A, 5-HT2C and 5-HT3 receptor. Intracerebroventricular infusion of 100 nmol 5-HT increased the extracellular hypothalamic concentration of vasopressin as measured by microdialysis in the PVN. To evaluate the involvement of hypothalamic-pituitary system in the 5-hydroxytryptophan and fluoxetine-induced vasopressin secretion, rats were immunoneutralized with a specific anti-corticotropin-releasing hormone antiserum. This treatment reduced plasma vasopressin and oxytocin responses. We conclude that stimulation with 5-hydroxytryptophan or 5-HT agonists increases mRNA expression of oxytocin in the PVN and the SON via stimulation of at least 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. Vasopressin mRNA in the PVN was increased only via the 5-HT2 receptor, whereas vasopressin mRNA in the SON does not seem to be affected by 5-HT stimulation. Corticotropin-releasing hormone appears to be partly involved in the mediation of 5-HT induced vasopressin and oxytocin secretion.
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PMID:Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides. 1271 7

The aim of the thesis was to investigate in male Wistar rats, the involvement of serotonin (5-HT) and 5-HT receptors in the regulation of the gene expression of hypothalamic hormones and in the secretion of the pituitary gland hormones prolactin (PRL), adrenocorticotropic hormone (ACTH), vasopressin (AVP) and oxytocin in basal and stress conditions. Furthermore, to study the significance of some distinctive central nuclei in these processes, and the metabolism of 5-HT in the hypothalamus and the dorsal raphe nucleus (DRN). The experiments were focused on (1) determination of involved neurons and nuclei (2) the hypothalamic level and (3) the pituitary gland level of regulation. The studies were typically performed in vivo but some studies were performed in vitro. Stereotactically neurotoxic lesion with 5,7-dihydroxy-5-HT in the dorsal raphe nucleus (DRN) or the hypothalamic paraventricular nucleus (PVN) reduced the ACTH and AVP response to stress, indicating an importance of these structures for this response. In situ hybridization on rat brain slices with oligopeptides showed an increase of corticotropin releasing hormone (CRH) mRNA in the PVN and proopiomelanocortin in the anterior pituitary lobe upon stimulation of the 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. Stimulation of 5-HT2A+2C receptors increased AVP mRNA in the PVN but not in the supraoptic nucleus (SON), whereas the level of oxytocin (OT) mRNA was increased both in the SON and the PVN and this effect was in addition mediated via 5-HT1A+1B receptors. Serotonin infused directly into the PVN by microdialysis stimulated local release of AVP. CRH was found to have a major role but not a complete responsibility in the 5-HT-induced release of ACTH, since immunoneutralisation of CRH inhibited the POMC gene expression and the ACTH response and since 5-HT and 5-HT antagonists were able to modulate the ACTH release from anterior pituitary gland cells in vitro. Through the years of investigation, the classification of the 7 main groups of 5-HT receptors (5-HT1 - 5-HT7) has changed due to molecular biological characterisation of the receptors and new receptors have been identified. With a battery of 5-HT agonists and antagonists several pharmacological experiments were performed with systemically or central administration of compounds and radioimmuno assay of plasma for pituitary gland hormone levels. Specific substances were not available for all 5-HT receptors and subreceptors thus some conclusions are a based on combination of experiments. The 5-HT induced PRL response is mediated via 5-HT1A, 5-HT2A, 5-HT2C and 5-HT3 receptors. In addition an involvement of 5-HT1B, 5-HT5 or 5-HT7 receptors seem possible. The ACTH response to 5-HT is mediated via 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors and an involvement of the 5-HT4, 5-HT5 and 5-HT7 receptors is proposed. Peripheral secretion of AVP upon stimulation with 5-HT is mediated via 5-HT2C, 5-HT4 and 5-HT7 receptors but not 5-HT1A receptors. The secretion of OT is primarily mediated via 5-HT1A, 5-HT2C and 5-HT4 receptors and probably also 5-HT1B, 5-HT2A, 5-HT5A and 5-HT7 receptors. Physical and psychological stress activates hippocampal and hypothalamic 5-HT neurons. In contrast to other stress factors, restraint stress increases the content of 5-HT in the DRN but do not increase the metabolism of 5-HT and does not induce changes in hypothalamic levels of 5-HT. Large variations are found in the literature with different kinds of stress, different measurements and different time schedules. Restraint or ether stress induced secretion of PRL involves 5-HT2 and 5-HT3 receptors, whereas the ACTH secretion is mediated via 5-HT1A, 5-HT2A and 5-HT2C receptors. In the present study restraint stress increased AVP secretion, but opposite findings has reported possibly due to differences in the stress procedure. The 5-HT2, 5-HT3 and 5-HT4 receptor is involved in the AVP response to restraint whereas the OT response involves the 5-HT1A and the 5-HT2 receptor. The 5-HT2 receptor is involved in the OT response to dehydration or haemorrhage, whereas the AVP responses to these stressors probably do not involve 5-HT. It can be concluded that 5-HT is involved in basal and stress-induced regulation of PRL, ACTH, AVP and oxytocin mainly via the 5-HT2A+2C receptors but other receptors are also important but differs from hormone to hormone. Serotonin affect the secretion of CRH and ACTH both at the hypothalamic, pituitary portal and pituitary gland level, and possibly also at the adrenal level.
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PMID:Studies on the neuroendocrine role of serotonin. 1820 78