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)

The development of vasopressin (AVP) receptors in the rat brain, spinal cord and pituitary gland was studied by in vitro light microscopic autoradiography. AVP binding sites were labeled using [3H]AVP in tissue sections from animals aged between embryonic day 12 (E12) and postnatal day 90 (PN90); the binding of [3H]AVP to oxytocin receptors was prevented by adding in the incubation medium a highly selective oxytocin agonist. Specific binding was first detected at E16 in the ventral pontine reticular formation. Many other brain areas were progressively labeled between E18 and PN5. The distribution of binding sites observed at PN5 remained unchanged until the beginning of the third postnatal week. Thereafter binding was markedly reduced or even disappeared in several areas, in particular in the facial nucleus. The adult distribution of AVP binding sites was established at the time of weaning. The properties of transient AVP binding sites in the facial nucleus were studied both by autoradiography and by electrophysiology. Non-radioactive AVP displaced [3H]AVP binding in this nucleus as efficiently as it did in the lateral septum of the adult. Single-unit extracellular recordings showed that AVP can excite facial motoneurones by interacting with receptors which are pharmacologically indistinguishable from V1 (vasopressor) type. Thus, AVP binding sites transiently expressed in the brain of fetal and infant rat probably represent functional neuronal receptors, having the same ligand selectivity and affinity than AVP binding sites present in the adult. This suggests that AVP acts not only as a neuropeptide in the adult brain but may play a significant role during maturation of the central nervous system.
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PMID:Early appearance and transient expression of vasopressin receptors in the brain of rat fetus and infant. An autoradiographical and electrophysiological study. 182 42

Oxytocin (OT)- and vasopressin (VP)-mRNAs were detected in the hypothalamus, during development, by in situ hybridization with synthetic oligonucleotide probes. The presence of VP- and OT-mRNAs was first detected in the supraoptic nucleus at E16 and E17 respectively, and simultaneously at E18 in the paraventricular nucleus. VP- (but not OT-) mRNA then appeared in the suprachiasmatic nucleus at E21, and OT- (but not VP-) mRNA, in the anterior commissural nucleus at time of birth. In the different nuclei, the relative distribution of cells containing OT- or VP-mRNA was comparable, from the earliest stages on, with that observed in the adult. These data suggest that the later appearance of mature OT (E20), versus VP (E16), reported in immunocytochemical studies, may not be due to a delayed transcription. Moreover, since the presence of both OT- and VP-prohormones has been reported at E16, the results support the idea of a rapid translation of both OT- and VP-mRNAs. In no location could OT- and VP-mRNAs be detected before final cell settlement; the possible role of environmental factors in final non-proliferative differentiation is discussed.
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PMID:Expression of the oxytocin and vasopressin genes in the rat hypothalamus during development: an in situ hybridization study. 270 68

The biosynthesis and posttranslational processing of arginine vasopressin (AVP) and oxytocin (OT) peptides in the developing rat brain and pituitary were studied using antibodies and complementary separation methods that permitted a quantitative radioimmunoassay (RIA) analysis of precursor, intermediate, and completely processed forms of the peptides. Precursor forms of the peptides were first detected in rat brain as early as embryonic day (E) 15 for AVP and E17 for OT. Proteolytic cleavage products of the precursors were detected 1 d later for both peptides. AVP was present in a fully processed (amidated) from immediately (E16) and throughout fetal development. OT was cleaved from its precursor starting on E18 but remained in an intermediate (C-terminal extended) form until E21, when amidated OT was first detected in the pituitary. Hence, Pro-AVP processing in the fetus was immediate and complete, whereas Pro-OT processing in the fetus was much slower and incomplete, resulting in the generation of partially processed, nonamidated stable forms of the peptide (OT-Gly10, OT-Gly10-Lys11, and OT-Gly10-Lys11-Arg12). The presence of OT-Gly10-Lys11-Arg12 as a major, stable intermediate form, indicated that the in vivo pattern of endoproteolytic cleavage occurred principally at the C-terminus of the pair of basic amino acids at the tripeptide spacer sequence (Gly-Lys-Arg) in the precursor. Although both precursors were first expressed nearly simultaneously in the brain, the steady-state levels of the precursors were very different throughout fetal life. From E16-E21, the quantities of AVP precursors and peptides were 5- to 10-fold greater than those of OT, suggesting a much higher level of precursor biosynthesis in the AVP neurons. In addition to these differences in the regulation of biosynthesis and processing, AVP peptides were axonally transported to the pituitary 3 d earlier than OT peptides, and in far greater (20-fold) abundance. The early presence and abundance of amidated AVP in the brain and pituitary suggests a trophic function for this peptide during development.
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PMID:Differential biosynthesis and posttranslational processing of vasopressin and oxytocin in rat brain during embryonic and postnatal development. 318 9

Two anti-neurophysin monoclonal antibodies (MABs), PS 36 and PS 41, described in the preceding paper (Ben-Barak, Y, J.T. Russell, M.H. Whitnall, K. Ozato, and H. Gainer (1985) J. Neurosci. 5:000-000), allowed us to specifically stain for oxytocin-associated neurophysin (NP-OT) or vasopressin-associated neurophysin (NP-AVP) in the hypothalamus of developing rats. Staining with these MABs specific for NP-OT or NP-AVP showed that both types of neurophysin appeared in cells in the developing hypothalamus as early as embryonic day (E16) and continued to increase in immunoreactivity throughout fetal life. The literature indicated that oxytocin appears in the system between E20 and E22, much later than vasopressin (E16 to E17), which we confirmed in immunocytochemical experiments using affinity-purified antisera to these hormones. Since the MABs recognize the specific prohormones as well as the specific mature neurophysins (Ben-Barak, Y., J. T. Russell, M.H. Whitnall, K. Ozato, and H. Gainer (1985) J. Neurosci. 5: 81-97), we conclude that there is a developmental delay between the synthesis of the oxytocin prohormone (pro-oxyphysin) and its processing to form oxytocin and NP-OT. The delay in prohormone processing in the oxytocin cells was correlated with a delay in immunocytochemically detectable neurites as compared to the vasopressin cells. This reduced level of axonal and dendritic immunoreactivity was still obvious in the oxytocin cells at 9 days after birth. In contrast, the clustering of cells to form adult-like hypothalamic nuclei appeared to follow similar time courses for the two types of cells. Adult-like distributions of cells staining for NP-OT and NP-AVP were already apparent in the supraoptic and paraventricular nuclei by E17.
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PMID:Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons. 388 Aug 14

The development of the hypothalamic vasopressin (VP) and oxytocin (OT) systems has been studied in rats from the 16th embryonic day (E16) until the 11th postnatal day (P11). The VP and OT mRNA-producing neurons were identified on cryostat sections by in situ hybridization using oligonucleotide probes labeled by [35S], [3H] or digoxigenin. Moreover, VP and OT gene expressions were evaluated either at E21 or at P11 following chronic depletion of catecholamines (CA). For this purpose, pregnant rats were daily injected with alpha-methyl-m(p)-tyrosine from gestational day 13 to 20 while neonates were daily injected with alpha-methyl-m(p)-tyrosine and neurotoxin 6-hydroxydopamine from postnatal day 2 to 10. No VP mRNA- or OT mRNA-expressing cells were observed in the hypothalamus of intact fetuses at E16, while 2 days later rather numerous VP and OT neurons occupied the anterior hypothalamus. One major bilateral group of VP and OT neurons was located in the supraoptic nucleus (SON). Less numerous labeled cells were found in the developing paraventricular nucleus (PVN). Some VP and OT neurons were also spread along the ventrolateral surface of the hypothalamus from the level of the median eminence, caudally, to the level of the optic nerves, rostrally. From E18 until birth, the OT neurons were localized in the dorsal portion of the SON, while its ventral portion was occupied by the VP neurons. The VP mRNA- and OT mRNA-expressing cells seemed to increase both in size and in number over the perinatal period. Frequent relatively long neuronal processes contained VP and OT mRNAs in fetuses and in newborns. When performed during the second half of the fetal life, the chronic depletion of CA did not cause any change in the VP and OT mRNA concentrations in the SON and PVN of fetuses. By contrast, similar treatment of neonates resulted in a significant increase of both mRNA levels in the SON. These data suggest that at least in the SON VP and OT gene expression might be under the inhibitory control of CA during the neonatal period.
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PMID:Vasopressin and oxytocin gene expression in intact rats and under catecholamine deficiency during ontogenesis. 763 91

The objective of this study was to determine the schedule of the arrival of the axons from the hypothalamus to the posterior lobe of the pituitary (PL) in rats during ontogenesis by using the fluorescent lipophilic carbocyanine dye 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI) as a retrograde tracer. After preliminary fixation of the brain, DiI crystals were implanted in the PL on embryonic day 15 (E15), E16, E17, and E19 as well as on postnatal day 2 (P2) and P9. This was followed by a DiI retrograde diffusion along the plasma membrane and subsequent staining of hypothalamic neuronal cell bodies. The supraoptic nucleus (SO) contained an accumulation of fluorescent cells that extended toward the diamond-like swelling of the third ventricle as early as E15. These data suggest that the magnocellular neurons of the SO send their axons to the PL at the very beginning of differentiation, perhaps even before reaching their final position. The initial axons of the neurons of the paraventricular nucleus proper (PV) appeared to reach the PL significantly later, at E17. In addition to the SO and the PV, accessory magnocellular nuclei contributed to the innervation of the PL in perinatal rats. The neurons of the retrochiasmatic accessory nucleus first sent their axons to the PL on E16-E17. Axons that originated from other accessory hypothalamic nuclei reached the PL after birth, suggesting a delay in their involvement in the regulation of visceral functions compared with other magnocellular nuclei. Thus, the axons of magnocellular neurons reach the PL unexpectedly early in embryogenesis, raising the possibility of the functional significance of vasopressin and oxytocin as fetal neurohormones.
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PMID:Projections from the hypothalamus to the posterior lobe in rats during ontogenesis: 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate tracing study. 1086 10

Correlated neuronal activity is instrumental in the formation of networks, but its emergence during maturation is poorly understood. We have used multibeam two-photon calcium microscopy combined with targeted electrophysiological recordings in order to determine the development of population coherence from embryonic to postnatal stages in the hippocampus. At embryonic stages (E16-E19), synchronized activity is absent, and neurons are intrinsically active and generate L-type channel-mediated calcium spikes. At birth, small cell assemblies coupled by gap junctions spontaneously generate synchronous nonsynaptic calcium plateaus associated to recurrent burst discharges. The emergence of coherent calcium plateaus at birth is controlled by oxytocin, a maternal hormone initiating labour, and progressively shut down a few days later by the synapse-driven giant depolarizing potentials (GDPs) that synchronize the entire network. Therefore, in the developing hippocampus, delivery is an important signal that triggers the first coherent activity pattern, which is silenced by the emergence of synaptic transmission.
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PMID:A parturition-associated nonsynaptic coherent activity pattern in the developing hippocampus. 1740 81

Monolayer cultures from hypothalami of embryonic, fetal and postnatal rats were established to study the development of oxytocin-secreting neurons in vitro. Particular culture conditions, known to enhance the survival and growth of different types of neural cells in vitro, were used to investigate the conditions necessary for the appearance and survival of these peptide-producing cells in culture. They included increasing the concentration of potassium in the culture milieu and/or the addition of triiodothyronine (T(3) ). The use of immunocytochemical procedures with a monoclonal antibody that recognizes oxytocin-associated neurophysin (NP-OT) and polyclonal antibodies specific for oxytocin permitted us to identify the neurons. In cultures derived from embryonic (E16-E17) hypothalami, no NP-OT- or oxytocin-positive neurons were detected and their appearance could not be provoked by increasing extracellular potassium concentration or by administration of T(3) . On the other hand, in cultures obtained from fetal (E18-E19) rat hypothalami, a few neurons showed immunoreactivity for NP-OT (but not for oxytocin); the immunoreactivity was localized essentially in somata and proximal portions of neurites. When 10(8) M T(3) was included in the culture medium, there were cells showing immunoreactivity not only for NP-OT, but also for oxytocin, visible in somata and in dendritic- and axonal-like processes. In comparison, T(3) did not influence the total number of neurons developing in these cultures. Lastly, in cultures derived from young postnatal (PO-P2) rat hypothalami, NP-OT- and oxytocin-immunopositive neurons were found regularly; their appearance did not require any special pretreatment of the cultures. In all cultures, high extracellular potassium concentration (25 mM) resulted in a general improvement in the survival of neurons but did not induce the appearance of more oxytocin-immunoreactive cells. Our observations support in vivo results showing that although presumptive oxytocin-producing cells appear early in the development of the hypothalamus, their maturation, and in particular, their ability to produce oxytocin, occurs late at the time of birth. A factor that selectively enhances their differentiation, is the thyroid hormone, T(3) .
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PMID:Development of oxytocinergic neurons in monolayer cultures derived from embryonic, fetal and postnatal rat hypothalami. 2155 27

Recent studies suggest that oxytocin (OXT) may be important for organising the neural circuitry that underlies adult social behaviour. Although most of the work exploring these effects has focused on early postnatal development, there is evidence that OXT may also be important during foetal development. However, without an understanding of how the OXT system develops, the ability to functionally link OXT in foetal life to adult behaviour is limited. To understand where and when OXT could be acting during embryonic development to affect the organisation of neural substrates, we examined the development of the mouse OXT system from embryonic day (E) 12.5 through postnatal day (PND) 2 using OXT receptor (OXTR) binding and a quantitative polymerase chain reaction. In both males and females, OXTR binding was observed by E16.5 in the ventricular and subventricular zones, as well as the developing amygdala. In males, OXT mRNA was not detectable until PND2, whereas it was detectable by E16.5 in females. OXTR mRNA was detected by E12.5 in both sexes, although females appear to have more OXTR mRNA during foetal development than males. The present study is significant because it is the first to reveal an unexpected sex difference in the development of the OXT system and supports the possibility that OXT during foetal development may contribute to sex differences in adult behaviour.
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PMID:Sex Differences in the Embryonic Development of the Central Oxytocin System in Mice. 2676 21