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

In addition to its secretion from neurohypophysial terminals, oxytocin (OT) is released within the hypothalamic magnocellular nuclei--the supraoptic (SON) and paraventricular nuclei--in response to various stimuli as mainly shown by microdialysis studies. During parturition and suckling, OT is released within the SON in a positive feedback role to further amplify its own local and/or neurohypophysial release depending upon the reproductive conditions. Whereas, for instance, intra-SON OT is important for appropriate OT secretion and milk ejection during suckling, it seems to be involved in the timing of the parturition process without directly affecting OT secretion during birth. As a consequence of various morphological and physiological adaptations of the OT system during lactation, the release pattern of OT into blood and within the SON is altered in response to other stimuli, like swim stress and peripheral osmotic stimulation. In addition, in lactating, but not virgin female or male rats, unilateral stimulation of the SON results in the release of OT, but not vasopressin or various amino acids, within the contralateral SON, which implicates a functional role of intranuclear OT in the plastic coupling of the paired SON during lactation. To manipulate OT synthesis and release, antisense targeting was used. Novel, acute effects (within 5 hours) of an OT antisense oligodeoxynucleotide on suckling-related parameters and, specifically, on the electrophysiological excitability of OT neurons as well as their ability to express the Fos-protein after CCK-8 are described. Since the OT content in the hypothalamo-neurohypophysial system was still unaffected at this time, antisense oligonucleotides may induce feedforward alterations in neuronal responsiveness which precede or parallel effects on neuropeptide synthesis. Taken together, the functional significance of OT released within the brain and into blood during reproduction provides an example of how a neuropeptide might regulate complex physiological and behavioral performances in a synergistic manner.
 ...
PMID:Release of oxytocin within the supraoptic nucleus. Mechanisms, physiological significance and antisense targeting. 871 62

The magnocellular oxytocin neurons within the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus are important relays in the milk ejection reflex in lactating animals, and are activated by suckling. It has been suggested that proto-oncogene transcription factors such as Fos/Jun act as early nuclear transducers of sensory stimuli in neurons. Therefore, we have studied with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal activity in the PVN and SON during suckling in lactating rats. In nonlactating rats, only few cells exhibiting FRAs were observed in these nuclei. Also in lactating rats subjected to continuous suckling Fos-like activity was low. In contrast, lactating rats separated from their pups for 4 h and then exposed to suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin and oxytocin neurons. Using in situ hybridization and immunohistochemistry we have also investigated the expression of the mRNAs for oxytocin, dynorphin, galanin and galanin message-associated peptide and of oxytocin and dynorphin in the PVN of lactating and nonlactating rats. In lactating rats, an increase in oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin and galanin message-associated peptide were downregulated. With the help of immunohistochemistry and double-staining methods, a substantial coexistence between oxytocin- and dynorphin-like immunoreactivities was shown in magnocellular neurons. These results indicate that FRAs are activated in the PVN in the beginning of a suckling period, while this response cannot be seen after continuous stimulation. Furthermore, in the PVN of lactating rats, an upregulation of oxytocin and dynorphin occurs while galanin expression decreases. Finally, the coexistence between oxytocin and dynorphin is more pronounced in lactating rats and nonlactating female rats than has previously been described in male rats.
 ...
PMID:Expression of Fos-related antigens, oxytocin, dynorphin and galanin in the paraventricular and supraoptic nuclei of lactating rats. 873 91

Angiotensin II (Ang) injected intracerebroventricularly stimulates neurohypophyseal vasopressin (AVP) release into the peripheral circulation. As we have shown previously, central actions of Ang II in the rat forebrain are mediated by the AT1A receptor subtype. In the present paper, we attempted to clarify the cellular localization of the AT1A receptor mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, in order to reappraise the conflicting data on the nature of the angiotensin II receptor involved in Ang induced vasopressin release. For this purpose, double in situ hybridization was performed using a radioactive AT1A receptor riboprobe and a digoxygenin labeled AVP oligoprobe, and immunohistochemical localization of the glial marker glial fibrillary acidic protein (GFAP) on the same brain slice. The results show neuronal expression of AT1A receptor mRNA mainly in dorsal and medial parvocellular parts of the PVN, its localization in some magnocellular PVN neurons and the absence of its expression in AVP producing neurons either in the PVN or in the SON. Thus, while indirect evidence indicates the involvement of the AT1A receptor subtype in the regulation of CRH and oxytocin release, the stimulation of vasopressinergic neurons is likely due to indirect mechanisms, or to a yet unknown type of angiotensin receptor.
 ...
PMID:Comparative expression of vasopressin and angiotensin type-1 receptor mRNA in rat hypothalamic nuclei: a double in situ hybridization study. 875 Aug 69

The magnocellular hypothalamic neurons exhibit a substantial degree of structural and functional plasticity over the time of pregnancy, parturition, and lactation. This study has used in situ hybridization techniques to examine whether the content of alpha 1, alpha 2, beta 2, gamma 2 GABAA receptor subunit mRNAs expressed by these cells fluctuates over this period. A process of regional, followed by cellular and then topographical, analyses within the supraoptic (SON) and posterior paraventricular (PVN) nuclei revealed that an increase in magnocellular alpha 1 subunit mRNA content occurred during the course of pregnancy up to day 19, after which a decline in expression was detected on the day of parturition. Significant fluctuations of this nature were observed only in the oxytocin neuron-enriched regions of the SON and PVN. The expression of alpha 2, beta 2, and gamma 2 subunit mRNAs in the SON and PVN and of all subunit mRNAs in the cingulate cortex did not change over this period. During lactation, gamma 2 subunit mRNA content within the PVN increased significantly on day 14 of lactation as compared with day 7, and topographical analysis suggested that it involved principally magnocellular vasopressin neurons. These results demonstrate the cell-and subunit-specific regulation of GABAA receptor mRNA expression within the hypothalamic magnocellular system. In particular, they suggest that fluctuations in alpha 1 subunit expression may contribute to the marked variations in electrical activity exhibited by magnocellular oxytocin neurons at the time of parturition. More generally, they provide evidence in support of GABAA receptor plasticity within a physiological context in the adult rat brain.
 ...
PMID:Plasticity in GABAA receptor subunit mRNA expression by hypothalamic magnocellular neurons in the adult rat. 875 19

1. It has been claimed that glutamate is the dominant excitatory neurotransmitter in neuroendocrine regulation. The evidence is derived mainly from in vitro experiments. 2. We have investigated in vivo a possible role of excitatory amino acids (EAAs) in the neural control of release of vasopressin (AVP) and oxytocin from the neurohypophysis. 3. In rats under ethanol anaesthesia in which a diuresis was maintained by a constant fluid load, the i.c.v. injection of glutamate and the synthetic agonists alpha-amino, 3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) produced an antidiuretic response (ADR) which was abolished by an AVP antagonist. For AMPA and NMDA it was shown that this ADR was accompanied by increased urinary excretion of AVP and oxytocin. 4. The selectivity of antagonists was tested in this system. D-2-Amino-5-phosphonopentanoate (D-AP5) blocked the responses to NMDA but not to AMPA; 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked the responses to both agonists. 5. The ADR to muscarine and hypertonic saline i.c.v., and the increase in excretion of AVP and oxytocin in response to muscarine, were blocked by CNQX but not by D-AP5. 6. The results suggest that hypertonic saline releases AVP and muscarine releases both AVP and oxytocin, at least in part, by activating a glutaminergic input to the SON and PVN involving an AMPA receptor. This input could function as a terminal interneurone in afferent neural pathways to these nuclei.
 ...
PMID:Release of vasopressin and oxytocin by excitatory amino acid agonists and the effect of antagonists on release by muscarine and hypertonic saline, in the rat in vivo. 878 84

Nitric oxide (NO) is produced by the enzyme NO synthase (NOS) and may be involved in the regulation of nutrient and endocrine homeostasis via actions on neurones of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. The effects of water deprivation or food deprivation for 4 days on the abundance of messenger RNA encoding NOS in these nuclei in rats were examined using in situ hybridization. Water deprivation markedly increased the abundance of NOS mRNA in both the SON and PVN (225 +/- 11% of control, P < 0.05 and 261 +/- 34% of control, P < 0.01 respectively). NOS mRNA abundance also appeared to be increased in magnocellular accessory nuclei. Food deprivation decreased NOS mRNA abundance in the SON and PVN (42 +/- 6% and 52 +/- 7% of control respectively, both P < 0.05), while withdrawal of both food and water produced no significant net changes in the abundance of NOS mRNA. Treatment-induced alterations in NOS mRNA abundance were reflected by changes in NOS activity, as assessed by NADPH-diaphorase histochemistry, and NADPH-diaphorase staining was observed in neurones both positive and negative for oxytocin-like immunoreactivity. These findings suggest that NOS mRNA abundance, NOS enzymatic activity and presumably NO production are modulated in an activity-dependent manner in hypothalamic (magnocellular and parvocellular) neurones by alterations in fluid and nutrient homeostasis, and support data from other studies suggesting a role for NO in the central regulation of water and food intake in the rat.
 ...
PMID:Food or water deprivation modulate nitric oxide synthase (NOS) activity and gene expression in rat hypothalamic neurones: correlation with neurosecretory activity? 880 71

Immunohistochemistry and morphometry were used to study the age-related changes in the vasopressin (AVP) and oxytocin (OXT) nerve cells in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei of 3-, 11- and 28-month-old rats. The results showed a statistically significant reduction in the mean number of AVP cells in the PVN, SON and SCN, and of OXT cells in the PVN with advancing age. Different age-related changes in the mean size of the immunoreactive cells were found in the three nuclei: a significant and transitory increase in the AVP and OXT cell sizes in the PVN, a tendency towards increasing the AVP and OXT cell sizes in the SON, and a significant and gradual decrease in the AVP cell size in the SCN. The combination of the morphometric data and staining patterns of the AVP and OXT perikarya and fibers in the PVN and SON pointed to an increased transport of AVP and OXT in 11-month-old rats as well as to a decreased production of these peptides in the PVN of 28-month-old rats. Taken together the staining pattern and the morphometric results showed a progressive loss of AVP cells in the SCN in aging.
 ...
PMID:Vasopressin- and oxytocin-immunoreactive nerve cells in the aging rat hypothalamus. 887 Aug 38

The hypothalamic peptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated as mediators of socio-sexual behaviors in addition to their roles in osmolar homeostasis (AVP), milk ejection and uterine contractility (OT). Within 24 h of parturition, OT and AVP messenger ribonucleic acid (mRNA) levels increase in the hypothalamic paraventricular, and to a lesser degree, the supraoptic nucleus (PVN and SON) of the rat. We previously reported that the prepartum increase in OT mRNA is related to the spontaneous decline in progesterone levels prior to parturition. We also reported that increases in PVN and SON OT mRNA can be induced by exposing the ovariectomized rat to a steroid regimen that mimics the steroid milieu of pregnancy, namely sequential estrogen and progesterone and subsequent progesterone withdrawal. Levels of PVN and SON AVP mRNAs were not affected by progesterone withdrawal in late pregnant rats or the steroid regimen that increased OT mRNA in ovariectomized rats. These observations suggest that other factors, perhaps hormonal, may influence AVP mRNA levels. A decline in testosterone coincident with waning progesterone levels also occurs prepartum. Since peak levels of AVP mRNA prepartum coincide with the prepartum decline in testosterone, we questioned whether declining testosterone levels are important for the increase in AVP mRNA levels. To examine a possible role for testosterone in the increased level of AVP mRNA in late pregnancy, we sequentially administered estradiol and testosterone long-term (2 weeks) and removed testosterone 48 h prior to sacrifice. This steroid regimen mimics the estrogen and testosterone pattern of late pregnancy in rats. AVP, but not OT, mRNA levels increased significantly in the PVN of ovariectomized rats receiving this steroid regimen. We also found that implantation of late pregnant rats with testosterone capsules to prevent the spontaneous prepartum decline in testosterone, attenuates the increase in PVN AVP, but not OT, mRNA on day 21 of pregnancy. The data show that sequential estrogen and testosterone and testosterone withdrawal increase the level of PVN AVP mRNA in the female rat.
 ...
PMID:Sequential exposure to estrogen and testosterone (T) and subsequent withdrawal of T increases the level of arginine vasopressin messenger ribonucleic acid in the hypothalamic paraventricular nucleus of the female rat. 891 Aug 10

The effects of osmotic stimulation on Fos expression and cell size increase in the supraoptic nucleus were evaluated in intact, sham-operated, and AV3V-lesioned rats. Fos-positive neurons were found mainly in the AV3V regions and the hypothalamic magnocellular neurons in the forebrain in dehydrated intact rats. Intraperitoneal injection of hypertonic saline and chronic dehydration induced a significant increase in number of Fos-positive neurons in the supraoptic nucleus of intact and sham-operated rats. AV3V lesions completely abolished the expression of Fos in SON neurons of rats that were intraperitoneally injected with hypertonic saline and were chronically dehydrated. Chronic dehydration increased significantly cell size of the OXT and AVP magnocelluar neurons in intact and sham-operated rats. However, there was no increase in cell size of those in the AV3V-lesioned rats. These results demonstrate that neural input derived from AV3V regions plays a significant role in causing Fos expression and structural changes such as cell size increase in the hypothalamic magnocellular neurons with osmotic stimulation.
 ...
PMID:Effect of AV3V lesions on Fos expression and cell size increases in magnocellular neurons of the rat hypothalamus during chronic dehydration. 895 77

The magnocellular oxytocin neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei play an important role in the initiation and maintenance of parturition in the rat. As little is known about the neural inputs responsible for activating oxytocin neuron activity at this time, we used the technique of microdialysis to examine the profile of monoamine and excitatory amino acid neurotransmitter release within the SON before and during parturition. Microdialysis probes were implanted into the SON of anesthetized pregnant rats (n = 8) on the morning of the day preceding parturition (day 20), and 15-min dialysate samples were collected from freely moving animals over the following 2 days until 3 h after birth of the last pup. On the day of parturition (day 21), dialysate concentrations of norepinephrine were significantly increased (P < 0.05) in the hour leading up to the expulsion of the first pup and, compared with those on the previous day, remained at significantly (P < 0.05) elevated levels throughout the course of parturition. A significant (P < 0.01) increase in glutamate concentrations was also detected, although in this case, it was only elevated transiently in the 15-min period immediately before the onset of pup expulsion. Mean levels of dopamine were not different between days 20 and 21, but a significant increase in dopamine release was detected specifically during the second half of parturition. No significant changes in serotonin and aspartate concentrations were observed on days 20 and 21 or in relation to parturition. This study provides an analysis of neurotransmitter release in the SON over parturition and indicates that norepinephrine concentrations are elevated well in advance of the onset of pup expulsion, whereas a burst of glutamate release occurs immediately before the birth of the first pup. Such changes are likely to reflect activity in afferent inputs to the SON and may represent neurochemical events involved in the initiation and maintenance of parturition.
 ...
PMID:Profile of monoamine and excitatory amino acid release in rat supraoptic nucleus over parturition. 897 82


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