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)

Prolactin (PRL) modulates maternal behavior and mediates hypothalamic pituitary adrenal axis inhibition during lactation via PRL receptors in the brain. To identify mechanisms mediating these effects, we examined the effects of PRL on signaling and CRH transcription in hypothalamic neurons in vivo and in vitro. Western blot of hypothalamic proteins from rats receiving intracerebroventricular PRL injection revealed increases in phosphorylation of the MAPK and ERK. Double-staining immunohistochemistry demonstrated phosphorylated ERK localization in parvocellular CRH neurons as well as magnocellular vasopressin and oxytocin neurons of the hypothalamic paraventricular (PVN) and supraoptic nuclei. PRL also induced ERK phosphorylation in vitro in the hypothalamic cell line, 4B, which expresses PRL receptors, and in primary hypothalamic neuronal cultures. Using reporter gene assays in 4B cells, or quantitative RT-PCR for primary transcript in hypothalamic cell cultures, PRL potentiated forskolin-stimulated CRH transcription through activation of the ERK/MAPK pathway. The effect of PRL in hypothalamic cell cultures was unaffected by tetrodotoxin, suggesting a direct effect on CRH neurons. The data show that PRL activates the ERK/MAPK pathway and facilitates CRH transcription in CRH neurons, suggesting that the inhibitory effect of PRL on hypothalamo-pituitary-adrenal axis activity reported in vivo is indirect and probably mediated through modulation of afferent pathways to the PVN. In addition, the prominent stimulatory action of PRL on the ERK/MAPK pathway in the hypothalamic PVN and supraoptic nucleus is likely to mediate neuroplasticity of the neuroendocrine system during lactation.
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PMID:Prolactin activates mitogen-activated protein kinase signaling and corticotropin releasing hormone transcription in rat hypothalamic neurons. 1902 92

Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and regulator of neuronal and glial plasticity in the brain. There is an increase in synthesis and release of PRL within the hypothalamus during peripartum and in response to stress. To identify mechanisms by which PRL induces neuroplasticity, we studied the ability of PRL to induce the transcription factor Egr-1 in the hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the hypothalamus in vivo. PRL induced Egr-1 mRNA expression in 4B cells, an effect which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular PRL (1 microg) increased Egr-1 mRNA levels in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled elevated Egr-1 protein expression in the PVN and SON. Double staining immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN, a population of non-oxytocin or vasopressin cells localized in a region corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1 immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic neurons, through MAP kinase-dependent induction of Egr-1.
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PMID:Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the rat hypothalamus. 1976 48

Animal studies have implicated the neuropeptides Prolactin (PRL) and Oxytocin (OT) in processes of maternal bonding and PRL has similarly been shown to play a role in the neurophysiology of fatherhood. Yet, very little is known on the involvement of PRL and OT in human fathering. Forty-three fathers and their firstborn infant were seen twice: in the second and sixth postpartum months. Paternal plasma PRL and OT were sampled at both time-points and analyzed with ELISA methods. At six months fathers were videotaped interacting with their child in social and exploratory play contexts and interactions were micro-analyzed for father-infant Affect Synchrony and father facilitation of child toy exploration. PRL and OT showed high individual stability across time and were correlated at the second observation. PRL was related to father-infant Coordinated Exploratory Play in the toy context whereas OT was associated with father-infant Affect Synchrony in the social context. Results point to the role of PRL and OT in the development of human fathering and underscore their differential relations with patterns of paternal care.
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PMID:Prolactin, Oxytocin, and the development of paternal behavior across the first six months of fatherhood. 2039 83

Prolactin (PRL) is one of the most versatile hormones in the mammalian body affecting reproductive, sexual, metabolic, immune, and other functions. It is therefore not surprising that the neural control of PRL secretion is complex, involving the coordinated actions of several hypothalamic nuclei. A plethora of experimental data exists on the hypothalamic control of hormone secretion under various physiological stimuli. There have been even mathematical models and computer studies published, which help to understand the complex hypothalamic-pituitary network. Nevertheless, the putative role of PRL for human reproduction still has to be clarified. Here, we review data on the underlying mechanisms controlling PRL secretion using both experimental and mathematical approaches. These investigations primarily focus on rhythmic secretion in rats during early pregnancy or pseudopregnancy, and they point to the important role of oxytocin as a crucial PRL-releasing factor. Recent data on human studies and their theoretical and clinical implications are reviewed as well. In particular, studies demonstrating a sustained PRL surge after sexual climax in males and females are presented, indicating possible implications for both sexual satiation and reproductive functions. Taking these data together, there is evidence for the hypothesis that the PRL surge induced by sexual activity, together with the altered PRL rhythmic pattern, is important for successful initialization of pregnancy not only in rodents but also possibly in humans. However, further investigations are needed to clarify such a role in humans.
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PMID:Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction. 2073 16

Neuropeptides of the brain are important neuromodulators, controlling behaviour and physiology. They signal through G protein-coupled receptors (GPCR) that couple to complex intracellular signalling pathways. These signalling networks integrate information from multiple sources, resulting in appropriate physiological and behavioural responses to environmental and internal cues. This paper will focus on the neuropeptides oxytocin and prolactin with respect to (1) the regulation of neuroendocrine stress responses and anxiety, and (2) the receptor-mediated molecular mechanisms underlying these actions of the neuropeptides. Besides its significant reproductive functions when released into the bloodstream, brain oxytocin reduces the activity of the hypothalamo-pituitary-adrenal (HPA) axis as well as anxiety-related behaviour in male and female rats. Oxytocin mediates its anxiolytic effect, at least in part, via binding to its GPCR in the hypothalamic paraventricular nucleus, followed by transactivation of the epidermal growth factor receptor, and subsequent activation of a MEK-extracellular signal-regulated kinase (ERK) MAP kinase pathway. Prolactin, by binding to its GPCR receptors, of which there are short and long forms, also activates ERK, and this is necessary for the control of the expression of corticotrophin-releasing hormone-an important regulator of the HPA axis. Liganded oxytocin and prolactin may also recruit other signalling pathways, but how these pathways contribute to the observed behavioural and physiological effects remains to be established. GPCR-mediated oxytocin and prolactin neuronal signalling are illustrative of the complexity of GPCR-activated regulation of appropriate neuroendocrine and behavioural responses to environmental and physiological demands.
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PMID:Bridging the gap between GPCR activation and behaviour: oxytocin and prolactin signalling in the hypothalamus. 2086 46

In nonhuman primates and humans, similar to other mammals, hormones are not strictly necessary for the expression of maternal behavior, but nevertheless influence variation in maternal responsiveness and parental behavior both within and between individuals. A growing number of correlational and experimental studies have indicated that high circulating estrogen concentrations during pregnancy increase maternal motivation and responsiveness to infant stimuli, while effects of prepartum or postpartum estrogens and progestogens on maternal behavior are less clear. Prolactin is thought to play a role in promoting paternal and alloparental care in primates, but little is known about the relationship between this hormone and maternal behavior. High circulating cortisol levels appear to enhance arousal and responsiveness to infant stimuli in young, relatively inexperienced female primates, but interfere with the expression of maternal behavior in older and more experienced mothers. Among neuropeptides and neurotransmitters, preliminary evidence indicates that oxytocin and endogenous opioids affect maternal attachment to infants, including maintenance of contact, grooming, and responses to separation. Brain serotonin affects anxiety and impulsivity, which in turn may affect maternal behaviors such as infant retrieval or rejection of infants' attempts to make contact with the mother. Although our understanding of the neuroendocrine correlates of primate maternal behavior has grown substantially in the last two decades, very little is known about the mechanisms underlying these effects, e.g., the extent to which these mechanisms may involve changes in perception, emotion, or cognition.
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PMID:The neuroendocrinology of primate maternal behavior. 2088 83

Prolactin (PRL) stimulates the secretion of oxytocin (OXT) and arginine AVP as part of the maternal adaptations facilitating parturition and lactation. Both neurohormones are under the regulation of nitric oxide. Here, we investigate whether the activation of neuronal nitric oxide synthase (nNOS) in the hypothalamo-neurohypophyseal system mediates the effect of PRL on OXT and AVP release and whether these effects operate in males. Plasma levels of OXT and AVP were measured in male rats after the intracerebroventricular injection of PRL or after inducing hyperprolactinemia by placing two anterior pituitary glands under the kidney capsule. NOS activity was evaluated in the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei by NADPH-diaphorase histochemistry and in hypothalamic extracts by the phosphorylation/inactivation of nNOS at Ser(847). Elevated central and systemic PRL correlated with increased NOS activity in the PVN and SON and with higher OXT and AVP circulating levels. Notably, treatment with 7-nitroindazole, a selective inhibitor of nNOS, prevented PRL-induced stimulation of the release of both neurohormones. Also, phosphorylation of nNOS was reduced in hyperprolactinemic rats, and treatment with bromocriptine, an inhibitor of anterior pituitary PRL secretion, suppressed this effect. These findings suggest that PRL enhances nNOS activity in the PVN and SON, thereby contributing to the regulation of OXT and AVP release. This mechanism likely contributes to the regulation of processes beyond those of female reproduction.
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PMID:Prolactin promotes oxytocin and vasopressin release by activating neuronal nitric oxide synthase in the supraoptic and paraventricular nuclei. 2094 59

Prolactin and oxytocin are important reproductive hormones implicated in several common adaptive functions during pregnancy, pseudopregnancy and lactation. Recently, extracellular recordings of supraoptic neurones have shown that prolactin may modulate the electrical activity of oxytocinergic neurones. However, no study has been conducted aiming to establish whether prolactin directly influences this activity in oxytocinergic paraventricular neurones. In the present study, we addressed this question by studying the effects of prolactin on the electrical activity and voltage-current relationship of identified paraventricular neurones in rat brain slices. Whole-cell recordings were obtained and neurones were classified on the basis of their morphological and electrophysiological fingerprint (i.e. magnocellular or parvicellular) and neuropeptide phenotype (i.e. oxytocinergic or non-oxytocinergic). We report that prolactin elicited a hyperpolarising current in 37% of the neurones in this nucleus, of which the majority (67%) were identified as putative magnocellular oxytocin neurones and the reminder (33%) were regarded as oxytocin-negative, parvicellular neuroendocrine neurones. Our results suggest that, in addition to the well-established negative feedback loop between prolactin-secreting lactotrophs and dopaminergic neurones in the arcuate nucleus, an inhibitory feedback loop also exists between lactotrophs and oxytocinergic paraventricular neurones.
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PMID:Prolactin induces a hyperpolarising current in rat paraventricular oxytocinergic neurones. 2185 27

Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA) neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum prolactin. Elevated prolactin levels during pregnancy and lactation may mediate actions in other hypothalamic regions such as the paraventricular nucleus (PVN) and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more sensitive prolactin targets than neurons in other regions because they are required to regulate basal prolactin secretion. Moreover, differences in the accessibility of the ARC to prolactin in blood may influence the responsiveness of this population. Therefore, we compared prolactin-induced signaling in different hypothalamic neuronal populations following either systemic or intracerebroventricular (icv) prolactin administration. Phosphorylation of the signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin-responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were widely observed in the ARC but absent from the rPOA and PVN. Many of these responsive cells in the ARC were identified as NEDA neurons. The lowest icv prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng) pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and appeared to be more sensitive than dopaminergic neurons in the rPOA. Subpopulations of oxytocin neurons in the hypothalamus were also found to be differentially sensitive to prolactin. These data suggest that differences in the accessibility of the arcuate nucleus to prolactin, together with intrinsic differences in the NEDA neurons, may facilitate homeostatic feedback regulation of prolactin release.
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PMID:Differential sensitivity of specific neuronal populations of the rat hypothalamus to prolactin action. 2195 90

In the female rat, a complex interplay of both stimulatory and inhibitory hypothalamic factors controls the secretion of prolactin. Prolactin regulates a large number of physiological processes from immunity to stress. Here, we have chosen to focus on the control of prolactin secretion in the female rat in response to suckling, mating and ovarian steroids. In all three of these states, dopamine, released from neurones in the mediobasal hypothalamus, is a potent inhibitory signal regulating prolactin secretion. Early research has determined that the relief of dopaminergic tone is not sufficent to account for the full surge of prolactin secretion observed in response to the suckling stimulus, launching a search for possible prolactin-releasing factors. This research has subsequently broadened to include searching for prolactin-releasing factors controlling prolactin secretion after mating or ovarian steroids. A great deal of literature has suggested that this prolactin-releasing factor may include oxytocin. Oxytocin receptors are present on lactotrophs. These oxytocin receptors respond to exogenous oxytocin and antagonism of endogenous oxytocin inhibits lactotroph activity. In addition, the pattern of oxytocin neuronal activity and oxytocin release correlate with the release of prolactin. Here, we suggest not only that oxytocin is stimulating prolactin secretion, but also that prolactin secretion is controlled by a complex network of positive (oxytocin) and negative (dopamine) feedback loops. We discuss the available literature and attempt to describe the circuitry we believe may be responsible for controlling prolactin secretion.
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PMID:Oxytocin: an emerging regulator of prolactin secretion in the female rat. 2212 99


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