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 plasma oxytocin (OT) response to acute stress was compared between virgin, lactating, and hyperprolactinaemic female rats. In virgin rats, brief immobilization was associated with a significant elevation of plasma OT to 24.7 +/- 3.7 pmol/l compared with 7.7 +/- 1.1 pmol/l in controls. In contrast, the stress response was absent in lactating (6 days post-partum) animals: control OT 9.4 +/- 2.2, immobilized OT 9.0 +/- 1.1 pmol/l. Hyperprolactinaemia produced by treatment with either dopamine antagonists (domperidone or haloperidol) or ovine prolactin was also associated with an impairment of the OT stress response in intact females, whereas domperidone treatment failed to modify the response in ovariectomized (OVX) rats. Following ovarian steroid replacement with oestradiol and progesterone, the inhibitory effect of domperidone was observed in OVX rats: control OT 11.1 +/- 2.5, immobilized OT 16.0 +/- 3.7 pmol/l. Treatment of OVX rats with oestradiol and progesterone, either separately or combined, did not modify the OT stress response. Plasma levels of vasopressin were not significantly modified in either control or immobilized rats of any experimental groups. The results indicate that hyperprolactinaemia may be a causative factor in the impairment of OT stress responses observed in lactating rats.
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PMID:Oxytocin responses to stress in lactating and hyperprolactinaemic rats. 369 84

Thirty-six puerperal women with inadequate lactation were treated with 50 mg sulpiride (N = 24) or placebo (N = 12) three times a day for two weeks. These treatments were supplemented with buccal oxytocin (100 IU, 300 IU, or 400 IU) or placebo preceding each breast-feeding on the sixth and 14th and on the seventh and 13th days of oral treatment, respectively. One woman treated with sulpiride and three women treated with placebo discontinued the trial because of the lack of the effect of treatment. The concentration of prolactin in maternal serum was higher (P less than .001) during sulpiride than placebo treatment at one week (380 +/- 43 ng/ml vs 23 +/- 7 ng/ml, mean +/- SE) and two weeks of treatment (381 +/- 38 ng/ml vs 34 +/- 10 ng/ml). Also, the daily breast milk yield, as measured objectively, was greater (P less than .05) during sulpiride than placebo treatment both at one week (628 +/- 51 ml vs 440 +/- 68 ml) and two weeks of treatment (684 +/- 67 ml vs 423 +/- 60 ml). Various doses of oxytocin failed to stimulate the milk secretion in the presence or absence of sulpiride-induced hyperprolactinemia. Thus, sulpiride improved inadequate lactation, whereas exogenous oxytocin alone or together with sulpiride had no effect on lactation in these mothers whose infants were able to suckle normally.
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PMID:Treatment of inadequate lactation with oral sulpiride and buccal oxytocin. 636 42

Targeted tumorigenesis, using the POMC gene promoter ligated to the simian virus 40 large T antigen, generated transgenic mice with massive tumors of the intermediate lobe (IL) of the pituitary. Inoculation of nude mice with the IL tumor cells resulted in very large secondary tumors. As the IL from several species produces a potent PRL-releasing factor (PRF), it was of interest to determine whether IL tumors from these mice also contain PRF. The objectives were to 1) measure serum PRL levels in mice with IL tumors, 2) determine whether these tumors contain PRF and examine its chromatographic properties, and 3) analyze whether this PRF is related to POMC, its derivatives, or other PRL secretagogues. Serum PRL levels were 5- to 6-fold higher in transgenic than in control mice. Primary and secondary IL tumors were acid extracted and successively fractionated using Sephadex G-100 gel filtration and reverse phase and gel permeation HPLC. PRF activity was determined using short term incubation of tissue extracts or column fractions with GH3 cells. Crude tumor extracts exhibited a strong and dose-dependent PRF activity. Upon chromatography, the PRF activity from either primary or secondary tumors resolved into two classes of compounds: a big PRF with an estimated mol wt of 70-80 kilodaltons and two small, very hydrophobic peptides. The elution profiles of the three PRFs differed from those of beta-endorphin, alpha MSH, beta MSH, ACTH, TRH, oxytocin, angiotensin II, vasoactive intestinal polypeptide, or corticotropin-like intermediate peptide. In summary, we have identified an animal model with IL tumors that has hyperprolactinemia and overproduces PRF. Two classes of PRFs, big and small, were resolved which differ from POMC derivatives and known regulators of PRL release. These data suggest that PRF is produced by melanotrophs, but is not a product of the POMC gene. The IL tumors should provide an excellent source for the purification and structural elucidation of PRFs.
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PMID:Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice. 778 36

Prolactin modulates maternal functions and is involved in behaviour. Binding sites have been identified in the hypothalamus and substantia nigra. Hyperprolactinaemia stimulates dopamine turnover in several areas of the brain, including the nucleus accumbens, and reduces turnover in other regions, e.g. the substantia nigra. Hyperprolactinaemia stimulates the opioidergic system. The portal concentration of dopamine and oxytocin (a prolactin stimulatory substance) may be increased in hyperprolactinaemia. In mammals, prolactin is associated with learning, stimulation of the immune response, reduction of body temperature and increased corticosterone secretion. It is involved in the behavioural aspect of reproduction. Secretion is strongly stimulated in the female rat on exposure to pups. Hyperprolactinaemia in male rats reduces sexual behaviour. Hyperprolactinaemia reduces libido in both men and women but in men it is also associated with low testosterone levels. There is evidence that in families characterized by an absent or alcoholic father young girls may be predisposed to develop hyperprolactinaemia later in life as a reaction to losses. The underlying mechanism of such a psychosomatic reaction, a typical example of which is pseudopregnancy, may be an extemporaneous activation of a neuroendocrine "maternal subroutine" characteristic of pregnancy. Prolactinomas may result from somatic changes occurring in activated lactotrophs.
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PMID:The psychogenic effects of prolactin. 837 7

The authors report the case of a 40-year-old woman with a 12-year history of irregular menses, amenorrhea, infertility, galactorrhea, a slightly elevated prolactin level, and a slowly growing pituitary adenoma. She developed recent onset of visual symptoms, prompting craniotomy for removal of an intrasellar tumor. Following surgery, her vision and prolactin levels returned to normal. Light microscopic and immunohistochemical examination of the tumor revealed it to be a neuroblastoma, which was immunohistochemically positive for synaptophysin, S-100 protein, and oxytocin. The neoplasm contained prolactin-positive neuroblastic and pituitary epithelial cells. No other pituitary hormones were found. Electron microscopy demonstrated two cell types: one with frequent neuritic processes containing neurosecretory granules and showing synaptic specialization, and another one compatible with epithelial adenohypophyseal cells. A few cells had ultrastructural features that were transitional between neuronal cells and granulated epithelial cells. Agranular folliculostellate cells were also identified. Immunoelectron microscopy demonstrated prolactin granules in the cytoplasm of the epithelial cells, in a few transitional cells, and in scattered neuritic processes. Ultrastructural and immunohistochemical features of the tumor suggested a transformation of pituitary epithelium to neuroblastic cells. Hyperprolactinemia and associated clinical symptoms may in part be attributed to selective prolactin secretion by neoplastic cells that were differentiating into adenomatous pituitary cells and, to a lesser extent, to cells differentiating into a neuroblastic line. Compression of pituitary stalk might also have been a contributory factor to the increased prolactin levels. Moreover, the oxytocin produced by the neuroblastic cells was considered an additional stimulus for prolactin secretion by neoplastic cells or by the normal pituitary.
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PMID:Differentiating neuroblastoma of pituitary gland: neuroblastic transformation of epithelial adenoma cells. Case report. 889 39

Prolactin (PRL) has been reported to promote antidiuresis and increase intestinal water-electrolyte absorption, whereas osmolar changes have been shown to influence PRL secretion. However, the mechanisms of action of PRL on the salt-water balance remain unclarified. The present clinical study targeted the effects of hyperprolactinaemia on the secretion of arginine-8-vasopressin (AVP), oxytocin (OXT) and cortisol. Plasma AVP and OXT were measured by radioimmunoassay, and cortisol by fluorimetry. In healthy women (21-39 y, n=6), an oral water load (OWL, 20 ml/bw) significantly suppressed the plasma levels of AVP, OXT and cortisol, and the PRL level too tended to decrease. In hyperprolactinaemic females (22-41 y, n=6, three with pituitary adenomas), water retention was registered following an OWL, together with paradoxical AVP and OXT level increases, whereas the cortisol response remained normal, and the PRL level did not change at all. Histamine (0.5 mg sc) stimulated the release of AVP, OXT and cortisol in the control and hyperprolactinaemic groups alike. These data suggest that alterations in AVP and OXT hypersecretion may contribute to the water retention in hyperprolactinaemia.
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PMID:Neurohypophysial hormone secretion in hyperprolactinaemic women. 984 4

The vital role played by prolactin during pregnancy and lactation is emphasized by the physiological adaptations that occur in the mother to maintain a prolonged state of hyperprolactinemia. In many species the placenta provides a source of lactogenic hormones in the circulation, ensuring the continued presence of a hormone capable of activating the prolactin receptor throughout pregnancy. In addition, the tuberoinfundibular dopamine neurons, which normally maintain a tonic inhibitory influence over prolactin secretion, show a reduced ability to respond to prolactin during late pregnancy and lactation, allowing high levels of prolactin to be maintained unopposed by a regulatory feedback mechanisms. There is clear evidence that systemic prolactin gains access to the cerebrospinal fluid, from where it can diffuse to numerous brain regions. Prolactin receptors are expressed in several hypothalamic nuclei, including the medial preoptic and arcuate nuclei, and we have observed marked increases in expression of prolactin receptors in these nuclei during lactation. Moreover, a number of hypothalamic nuclei, including the paraventricular, supraoptic and ventromedial nuclei, in which prolactin receptors were not detected in diestrous rats, were found to express significant amounts of prolactin receptor during lactation. These observations have important implications for the variety of documented actions of prolactin on the brain. Prolactin has been reported to influence numerous brain functions, including maternal behavior, feeding and appetite, oxytocin secretion, and ACTH secretion in response to stress. In light of the high circulating levels of prolactin during pregnancy and lactation and the increased expression of prolactin receptors in the hypothalamus, many of these effects of prolactin may be enhanced or exaggerated during lactation. Hence, prolactin may be a key player in the coordination of neuroendocrine and behavioral adaptations of the maternal brain.
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PMID:The actions of prolactin in the brain during pregnancy and lactation. 1158 28

The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon.
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PMID:From galactorrhea to osteopenia: rethinking serotonin-prolactin interactions. 1499 75

Chronic intracerebroventricular (icv) infusion of prolactin (PRL) into the cerebral ventricles and mimicking central hyperprolactinemia in lactation has recently been shown to reduce anxiety and neuronal as well as neuroendocrine responses to acute stressor exposure. Here, we studied the effects of icv PRL on the activity of the oxytocin (OXT) and arginine vasopressin (AVP) systems of virgin female, ovariectomized, estradiol-substituted Wistar rats. Ovine PRL was delivered via osmotic minipumps at 0.01, 0.1 or 1 microg/h for 5 days. Under basal conditions, both plasma OXT and AVP concentrations were increased after chronic PRL treatment (1 microg/h). At hypothalamic level, this was accompanied by an increased c-fos and OXT mRNA expression within the supraoptic nucleus, the main source of plasma OXT, whereas AVP mRNA levels remained unchanged. No effect of PRL on c-fos or on nonapeptide mRNA expression was found in the hypothalamic paraventricular nucleus. Moreover, chronic PRL abolished the rise in plasma OXT induced by acute exposure to 30 min restraint stress in vehicle-treated rats. However, restraint stress did not significantly alter OXT or AVP mRNA expression in the hypothalamus of either vehicle- or PRL-treated animals. From these results we conclude that brain hyperprolactinemia alters the synthetic activity of OXT neurons and the secretory performance of OXT and AVP neurons within the hypothalamus, resulting in elevated plasma concentrations of both hormones under basal conditions. These changes are comparable to adaptations seen in the female peripartum period.
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PMID:Effects of chronic intracerebral prolactin on the oxytocinergic and vasopressinergic system of virgin ovariectomized rats. 1954 17

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


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