Showing papers on "Oxytocin published in 1998"
TL;DR: The long-term lowering of blood pressure and of cortisol levels as well as the sedative effects of oxytocin have been found to be related to an increased activity of central alpha 2-adrenoceptors, which may explain the health-promoting effects of certain alternative therapies.
834 citations
TL;DR: These findings provide the first evidence for a direct interaction between a steroid hormone and a G-protein-coupled receptor and define a new level of crosstalk between the peptide- and steroid-hormone signalling pathways.
Abstract: The steroid hormone progesterone (P4) is essential for establishing and maintaining pregnancy in mammals. One of its functions includes maintenance of uterine quiescence by decreasing uterine sensitivity to the uterotonic peptide hormone oxytocin. Although it is generally held that steroid hormones such as P4 act at a genomic level by binding to nuclear receptors and modulating the expression of specific target genes, we show here that the effect of P4 on uterine sensitivity to oxytocin involves direct, non-genomic action of P4 on the uterine oxytocin receptor (OTR), a member of the G-protein-coupled receptor family. P4 inhibits oxytocin binding to OTR-containing membranes in vitro, binds with high affinity to recombinant rat OTR expressed in CHO cells, and suppresses oxytocin-induced inositol phosphate production and calcium mobilization. These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone. Our findings provide the first evidence for a direct interaction between a steroid hormone and a G-protein-coupled receptor and define a new level of crosstalk between the peptide- and steroid-hormone signalling pathways.
475 citations
TL;DR: The results indicate that the reduced response of the HPA axis to stressors described previously during lactation is already manifested around day 15 of pregnancy in the rat and involves physiological adaptations at the adenohypophysial level.
Abstract: 1. The responsiveness of the rat hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-neurohypophysial system (HNS) to emotional (elevated plus-maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin-releasing hormone (CRH) was investigated during pregnancy and lactation. In addition to pregnancy-related adaptations at the adenohypophysial level, behavioural responses accompanying the neuroendocrine changes were studied. 2. Whereas basal (a.m.) plasma corticosterone, but not corticotrophin (adrenocorticotrophic hormone; ACTH), levels were increased on the last day (i.e. on day 22) of pregnancy, the stress-induced rise in both plasma hormone concentrations was increasingly attenuated with the progression of pregnancy beginning on day 15 and reaching a minimum on day 21 compared with virgin control rats. A similar attenuation of responses to both emotional and physical stressors was found in lactating rats. 3. Although the basal plasma oxytocin concentration was elevated in late pregnancy, the stress-induced rise in oxytocin secretion was slightly lower in day 21 pregnant rats. In contrast to vasopressin, oxytocin secretion was increased by forced swimming in virgin and early pregnant rats indicating a differential stress response of these neurohypophysial hormones. 4. The blunted HPA response to stressful stimuli is partly due to alterations at the level of corticotrophs in the adenohypophysis, as ACTH secretion in response to CRH in vivo (40 ng kg-1, i.v.) was reduced with the progression of pregnancy and during lactation. In vitro measurement of cAMP levels in pituitary segments demonstrated reduced basal levels of cAMP and a lower increase after CRH stimulation (10 nM, 10 min) in day 21 pregnant compared with virgin rats, further indicating reduced corticotroph responsiveness to CRH in pregnancy. 5. The reduced pituitary response to CRH in late pregnancy is likely to be a consequence of a reduction in CRH receptor binding as revealed by receptor autoradiography. [125I] CRH binding in the anterior pituitary was significantly reduced in day 11, 17 and 22 pregnant rats compared with virgin controls. 6. Anxiety-related behaviour of the animals as revealed by the time on and entries into the open arms of the elevated plus-maze was different between virgin and pregnant rats with decreased number of entries indicating increased anxiety with the progression of pregnancy (except on pregnancy day 18). The emotional behaviour, however, was not correlated with the neuroendocrine responses. 7. The results indicate that the reduced response of the HPA axis to stressors described previously during lactation is already manifested around day 15 of pregnancy in the rat and involves physiological adaptations at the adenohypophysial level. However, alterations in stressor perception at higher brain levels with the progression of pregnancy may also be involved.
367 citations
TL;DR: Release patterns measured before, during and after repeated stress exposure on three consecutive days indicated that, at the level of the hypothalamus, the two neuropeptides are critically involved in the rats' stress response in a peptide-, locus- and stress-specific manner.
353 citations
TL;DR: Spatial and temporal differences between peptide release within the nuclei and that from the distant axonal varicosities indicate that the release mechanisms are at least partially independent, supporting the hypothesis of locally regulated dendritic release of vasopressin and oxytocin.
Abstract: In addition to the release of neurotransmitters from their axon terminals, several neuronal populations are able to release their products from their dendrites. The cell bodies and dendrites of vasopressin- and oxytocin-producing neurones are mainly located within the hypothalamic supraoptic and paraventricular nuclei and neuropeptide release within the magnocellular nuclei has been shown in vitro and in vivo. Local release is induced by a range of physiological and pharmacological stimuli, and is regulated by a number of brain areas; locally released peptides are mainly involved in pre- and postsynaptic modulation of the electrical activity of magnocellular neurones. Spatial and temporal differences between peptide release within the nuclei and that from the distant axonal varicosities indicate that the release mechanisms are at least partially independent, supporting the hypothesis of locally regulated dendritic release of vasopressin and oxytocin. In this respect, magnocellular neurones show similarities to other neuronal populations and thus autoregulation of neuronal activity by dendritic neuromodulator release may be a general phenomenon within the brain.
327 citations
TL;DR: Recent studies suggest that the vasopressin V1b receptor may serve additional and unknown functions in the brain and at the periphery, and a great number of molecular probes have been developed, including agonists and antagonists, and radiolabelled, fluorescent or photosensitive ligands.
Abstract: The neurohypophyseal hormones vasopressin and oxytocin are two closely related nonapeptides, synthesized mainly by the magnocellular neurons of the hypothalamus. Their peptide sequences differ only in the amino acids at positions 3 and 8, but, for both hormones, the formation of a disulfide bond between Cys residues at the 1 and 6 positions results in a peptide constituted of a 6 amino acid cyclic part and a 3 amino acid C-terminal part. Both peptides exert various hormonal effects. Circulating oxytocin is mostly known for its ability to elicit the contraction of uterine smooth muscle at term and that of myoepithelial cells that surround the alveoli of the mammary gland during lactation. The main endocrine functions of arginine vasopressin (AVP) are the facilitation of water reabsorption by the kidney and the contraction of smooth muscle cells in arteries. AVP released in the portal blood in the median eminence acts as a potent secretagogue of adrenocorticotropin. In addition, it has become clear that vasopressin and oxytocin, besides mediating well-documented functions at the periphery, are also critically involved in numerous central processes including higher cognitive functions such as memory and learning (see Barberis & Tribollet 1996 for review). Vasopressin and oxytocin were the first biologically active peptides to be synthesized. This achievement, by Du Vigneaud and coworkers, 40 years ago, ushered in the modern era of peptide chemistry. During the subsequent decades, many structural analogues of the neurohypophyseal hormones have been synthesized and pharmacologically characterized (Manning & Sawyer 1993). Peripheral vasopressin and oxytocin receptors have been classified on the basis of both the second messenger system coupled to the receptors and the affinity of a series of vasopressin and oxytocin analogues with enhanced selectivity for a certain receptor type. These classification criteria have led to the distinction of V1a vasopressin (liver, smooth muscle cells from blood vessels, and most peripheral tissues expressing vasopressin receptors), V1b vasopressin (adenohypophysis), V2 vasopressin (kidney) and oxytocin (uterus, mammary gland) receptors ( Jard et al. 1988). To date central receptors have been identified as being of the vasopressin V1a and oxytocin subtypes. Moreover, a great number of molecular probes have been developed, including agonists and antagonists, and radiolabelled, fluorescent or photosensitive ligands. These make this receptor family a good model with which to study structure–function relationships. Today, the four different receptor subtypes have been cloned in mammals, lower vertebrates and invertebrates. Molecular cloning studies have renewed interest in these neurohormone receptors. Vasopressin V1b receptor mRNA has been detected in peripheral tissues (kidney, thymus, heart, lung, spleen, uterus and breast) and numerous areas of the brain in the rat (Lolait et al. 1995), and this receptor subtype has also been characterized in rat adrenal (Grazzini et al. 1996). These studies suggest that the vasopressin V1b receptor may serve additional and unknown functions in the brain and at the periphery. The primary focus of this review is to summarize recent studies that have led to novel insights into the molecular bases of vasopressin and oxytocin receptor functions.
293 citations
TL;DR: During machine-milking, the physiological requirements of the cows need to be considered, and, most importantly, stressors must be minimized.
246 citations
TL;DR: It is demonstrated that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.
Abstract: Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2α production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2α production. These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.
234 citations
TL;DR: The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitricoxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.
220 citations
TL;DR: The findings suggest that estrogen can directly modulate specific OT and AVP systems through an ERbeta-mediated mechanism, in a tissue-specific manner.
Abstract: Evidence exists for the localization of the newly identified estrogen receptor β (ERβ) within the rat paraventricular nucleus (PVN) and supraoptic nucleus (SON), regions which lack ERα. Presently, we investigate whether ERβ-like-immunoreactivity (-ir) is found within cells of several major neuropeptide systems of these regions. Young adult Sprague–Dawley rats were ovariectomized (OVX), and 1 week later half of the animals received estradiol-17β (E). Dual-label immunocytochemistry was performed on adjacent sections by using an ERβ antibody, followed by an antibody to either oxytocin (OT), arginine-vasopressin (AVP), or corticotropin releasing hormone. Nuclear ERβ-ir was identified within SON and retrochiasmatic SON, and in specific PVN subnuclei: medial parvicellular part, ventral and dorsal zones, dorsal and lateral parvicellular parts, and in the posterior magnocellular part, medial and lateral zones. However, the ERβ-ir within magnocellular areas was noticeably less intense. OT-/ERβ-ir colocalization was confirmed in neurons of the parvicellular subnuclei, in both OVX and OVX+E brains (≈50% of OT and 25% of ERβ-labeled cells between bregma −1.78 and −2.00). In contrast, few PVN parvicellular neurons contained both AVP- and ERβ-ir. As well, very little overlap was observed in the distribution of cells containing corticotropin releasing hormone- or ERβ-ir. In the SON, most nuclear ERβ-ir colocalized with AVP-ir, whereas few OT-/ERβ-ir dual-labeled cells were observed. These findings suggest that estrogen can directly modulate specific OT and AVP systems through an ERβ-mediated mechanism, in a tissue-specific manner.
219 citations
TL;DR: The finding of abundant OT receptor in atrial myocytes supports the hypothesis that OT, directly and/or via atrial natriuretic peptide release, can regulate the force of cardiac contraction and suggests an autocrine and or paracrine role for the peptide.
Abstract: We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 ± 114 pg/mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the effluent of isolated, perfused rat heart (34.5 ± 4.7 pg/min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription–PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart’s chambers suggests an autocrine and/or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and/or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.
TL;DR: Little is known of, and more has to be done to identify, the neurochemical mechanisms underlying yawning at the central level, as this short overview of the literature on the neurochemistry of yawning shows.
TL;DR: Results show that OT, but not VP, is released into the PVN and peripheral blood in response to shaker stress, raising the possibility that local release of OT into the solar plexus plays a role in the neuroendocrine stress cascade.
TL;DR: The results demonstrate that the highest cellular levels of ER-β messenger RNA (mRNA) in OT-IR neurons can be visualized in the caudal portion of the PVN and in an area ventro-medial to the central core of VP-IR cells.
Abstract: The regulatory actions of estrogen on magnocellular oxytocin (OT) and vasopressin (VP) neurons of the paraventricular (PVN) and supraoptic (SON) nuclei are well documented. To date it is still debated whether the effect of estrogens is exerted directly or mediated by estrogen-sensitive interneurons. Previous immunocytochemical (ICC) and in situ hybridization (ISH) studies detected either low levels or absence of the classical estrogen receptor (ER-alpha) in the PVN and the SON of the rat. The present experiments using a combined ICC and ISH method were undertaken to examine the expression of the recently cloned beta form of ER (ER-beta) in OT- and VP-immunoreactive (IR) neuronal systems of the rat hypothalamus. The results demonstrate that the highest cellular levels of ER-beta messenger RNA (mRNA) in OT-IR neurons can be visualized in the caudal portion of the PVN and in an area ventro-medial to the central core of VP-IR cells. These neurons were previously shown to project caudally to the brain stem and the spinal cord to regulate autonomic functions. In addition, the whole rostro-caudal extent of the PVN and the SON contained OT-IR neurons that coexpressed variable levels of ER-beta mRNA. Similarly, the presence of ER-beta mRNA was seen in a large population of VP-IR paraventricular and supraoptic neurons. In the SON, somewhat stronger hybridization signal was detected in VP-IR neurons as compared with OT-IR neurons. Together, these findings provide strong support for the concept that the functions of OT- and VP-IR neurons in the PVN and the SON are regulated directly by estrogen and that the genomic effects of estrogens are mediated by ER-beta.
TL;DR: It is demonstrated that ERalpha is not necessary for basal OTR synthesis, but is absolutely necessary for the induction of OTR binding in the brain by estrogen.
Abstract: The induction of oxytocin receptor (OTR) synthesis in the periphery and in the brain by estrogen is critical for reproductive success. Oxytocin receptors are involved in the control of parturition, milk ejection, and sexual and maternal behaviors. The discovery of a second estrogen receptor (ERbeta) in the brain and the failure of in vitro transcription studies using OTR promoter constructs to replicate the in vivo transcriptional regulation have raised questions regarding the molecular mechanisms involved in the regulation of the OTR gene by estrogen. Using mice genetically deficient in estrogen receptor alpha (ERalpha), we demonstrate that ERalpha is not necessary for basal OTR synthesis, but is absolutely necessary for the induction of OTR binding in the brain by estrogen.
TL;DR: Repeated oxytocin injections cause lowered blood pressure, decreased cortisol levels, increased withdrawal latency, increased release of vagally controlled gastrointestinal hormones, and increased weight gain, which form an antistress pattern.
Abstract: Repeated oxytocin injections cause lowered blood pressure, decreased cortisol levels, increased withdrawal latency, increased release of vagally controlled gastrointestinal hormones, and increased weight gain. Together, these effects form an antistress pattern. Nonnoxious sensory stimuli release oxytocin and induce an effect spectrum similar to the one caused by oxytocin injections.
TL;DR: The results demonstrate that the olfactory bulb represents an additional important central nervous system target site where these peptides can act to preserve social recognition responses and suggest that the underlying mechanisms by which peptides function within the ofalactory bulb differ as a function of whether they are involved with the display versus preservation of recognition responses.
TL;DR: In both types of oxytocin gene disablement, the only evident defect was a complete failure of postpartum homozygotes to transfer milk to the suckling young, which consequently did not survive unless the mothers were treated with exogenous oxytocIn, and these findings are surprising in view of the vast literature on a wide range of species suggesting important roles for oxytoc in regulating gonadal function, in expression of sexual behaviour, in parturition and initiation of maternal behaviour as well as
Abstract: Our understanding of the functions of oxytocin in mammals has recently been challenged by findings in transgenic mice in which the oxytocin gene has been knocked out. Mammals generally have only two posterior pituitary nonapeptide genes, for oxytocin and vasopressin, while some marsupials do not express oxytocin but do express a closely related peptide, mesotocin, which acts at the oxytocin receptor (Acher et al. 1995). Birds have arginine vasotocin and mesotocin (Acher et al. 1995), while among other vertebrates a subclass of cartilaginous fishes evidently produces oxytocin (Michel et al. 1993). Mice homozygous for deletion of exon 1 of the oxytocin gene, containing the oxytocin nonapeptide sequence, were produced by homologous recombination in mouse embryonic stem cells. Offspring from matings of the heterozygotes were in the correct Mendelian frequency, indicating no lethal developmental defects in the homozygotes, which later showed normal sexual maturation, with both males and females showing sexual behaviour and normal fertility (Nishimori et al. 1996). Young and colleagues (1996) used gene targeting to generate a mouse with most of the first intron and the last two of the three exons of the oxytocin gene eliminated. The amount of oxytocin gene transcripts in the supraoptic and paraventricular nuclei of homozygotes was 1% of the wild-type level, with less than 0·4% of the wild-type content of oxytocin in the pituitary gland, and no oxytocin detectable in blood plasma by RIA. In both types of oxytocin gene disablement, the only evident defect was a complete failure of postpartum homozygotes to transfer milk to the suckling young, which consequently did not survive unless the mothers were treated with exogenous oxytocin. Thus parturition and maternal behaviour proceeded without oxytocin, although these processes were not studied in detail. These findings are surprising in view of the vast literature on a wide range of species suggesting important roles for oxytocin in regulating gonadal function, in expression of sexual behaviour, in parturition and initiation of maternal behaviour as well as in lactation. It is appropriate to consider whether the results from the oxytocin knockout mice arise from peculiarities in the roles of oxytocin in the mouse in comparison with other species, or indicate redundancy in the mechanisms in which oxytocin normally has an important role; apart that is, from the milk-ejection reflex in which there is no evident redundancy, at least in the mouse.
TL;DR: Female Wistar rats tested for juvenile discrimination abilities suggest that within a narrow range of concentrations endogenous oxytocin, but not vasopressin, is critically involved in short-term olfactory memory for juvenile conspecifics in female rats.
TL;DR: The unique promoter sequences of the prairie vole OTR and V1a receptor genes and the resulting species-specific pattern of regional expression provide a potential molecular mechanism for the evolution of pair bonding behaviors and a cellular basis for monogamy.
Abstract: Several lines of evidence support a role for oxytocin and vasopressin in complex social behaviors, including parental care, sex behavior, and aggression. Recent studies in a monogamous mammal, the prairie vole, suggest an additional role for both peptides in the formation of pair bonds. Central administration of oxytocin facilitates and administration of an oxytocin antagonist inhibits partner preference formation in female prairie voles. Conversely, vasopressin facilitates and a V1a receptor antagonist inhibits pair bonding in males. A potential cellular basis for these effects is the species-specific pattern of expression of oxytocin and V1a receptors in reward pathways of the prairie vole brain. At a molecular level, comparative sequencing of the oxytocin and V1a receptors reveals species differences in the promoter sequences that may guide regional expression in the brain. Transgenic mice created with the 5’ flanking region of the prairie vole oxytocin receptor gene demonstrate that sequences in this region influence the pattern of expression within the brain. The unique promoter sequences of the prairie vole OTR and V1a receptor genes and the resulting species-specific pattern of regional expression provide a potential molecular mechanism for the evolution of pair bonding behaviors and a cellular basis for monogamy.
TL;DR: The authors' data indicate that magnocellular neurons of the paraventricular nucleus of the PVN receive excitatory inputs from intranuclear glutamatergic neurons that express α1-adrenoreceptors, which may serve as an excited relay in the afferent noradrenergic control of oxytocin and vasopressin release under certain physiological conditions.
Abstract: Noradrenergic projections to the hypothalamus play a critical role in the afferent control of oxytocin and vasopressin release. Recent evidence for intrahypothalamic glutamatergic circuits prompted us to test the hypothesis that the excitatory effect of noradrenergic inputs on oxytocin and vasopressin release is mediated in part by local glutamatergic interneurons. The voltage response to norepinephrine (30–300 μm) was tested with whole-cell recordings in putative magnocellular neurons of the paraventricular nucleus (PVN) in hypothalamic slices (400 μm). Norepinephrine elicited an α1 receptor-mediated direct depolarization in 23% of the magnocellular neurons tested; however, the most prominent response, seen in 42% of the magnocellular neurons, was an α1receptor-mediated increase in the frequency of EPSPs. The norepinephrine-induced increase in EPSPs was blocked by tetrodotoxin and by ionotropic glutamate receptor antagonists, suggesting that norepinephrine excited presynaptic glutamate neurons to cause an increase in spike-mediated transmitter release. The increase in EPSPs also was observed in a surgically isolated PVN preparation (64% of cells) and with microdrop applications of norepinephrine (1 mm, 33% of cells) and glutamate (0.5–1 mm, 28%) in the PVN, indicating that the norepinephrine-sensitive presynaptic glutamate neurons are located within the PVN. Biocytin injection and subsequent immunohistochemical labeling revealed that both oxytocin and vasopressin neurons responded to norepinephrine. Our data indicate that magnocellular neurons of the PVN receive excitatory inputs from intranuclear glutamatergic neurons that express α1-adrenoreceptors. These glutamatergic interneurons may serve as an excitatory relay in the afferent noradrenergic control of oxytocin and vasopressin release under certain physiological conditions.
TL;DR: Data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle.
Abstract: The transport function of the uterus and oviducts and its modulation by oxytocin has been examined using hysterosalpingoscintigraphy, recording of intrauterine pressure, electrohysterography and Doppler sonography of the Fallopian tubes After application to the posterior vaginal fornix, a rapid (within minutes) uptake of the labelled particles into the uterus was observed during the follicular and during the luteal phase of the cycle in all patients Transport into the oviducts, however, could only be demonstrated during the follicular phase Transport was directed predominantly into the tube ipsilateral to the ovary bearing the dominant follicle; the contralateral oviduct appeared to be functionally closed The proportion of patients exhibiting ipsilateral transport did increase concomitant with the increase of the diameter of the dominant follicle That ipsilateral transport has biological significance is suggested by the observation that the pregnancy rate following spontaneous intercourse or insemination was significantly higher in those women in whom ipsilateral transport could be demonstrated than in those who failed to exhibit lateralization Oxytocin administration was followed by a dramatic increase in the amount of material transported to the ipsilateral tube, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium Continuous recording of intrauterine pressure before and after oxytocin administration did show an increase in basal tonus and amplitude of contractions and a reversal of the pressure gradient from a fundo-cervical to a cervico-fundal direction These actions of oxytocin were accompanied by an increase in amplitude of potentials recorded by electrohysterography These data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle In addition, they strongly suggest a critical role of oxytocin in this process Failure of this mechanism appears to be a cause of subfertility or infertility, as indicated by the low pregnancy rate following intrauterine insemination or normal intercourse in the presence of patent Fallopian tubes It may be regarded as a new nosological entity for which we propose the term tubal transport disorder (TTD) Since pregnancy rate of such patients is normal when treated with in-vitro fertilization (IVF), hysterosalpingoscintigraphy seems to be useful for the choice of treatment modalities in patients with patent Fallopian tubes suffering from infertility
TL;DR: In this article, the authors showed that glucocorticoids suppress both CRH and vasopressin (AVP) neurons in the human hypothalamus, which may have important consequences for neuroendocrinological mechanisms such as the disturbance of water balance during treatment as well as the immunological processes in the brain and the pathogenesis of the withdrawal syndrome after discontinuation of corticosteroid treatment.
Abstract: Glucocorticoids are widely used in clinical practice in a variety of immune-mediated and neoplastic diseases, mostly for their immunosuppressive, leukopenic, antiedematous, or malignancy-suppressive actions. However, their usage is limited because of serious and sometimes life-threatening side-effects. Endogenous glucocorticoids are secreted by the adrenal cortex under the control of the hypothalamus and the pituitary gland. This hypothalamo-pituitary-adrenal axis, in turn, is under the negative feedback control of glucocorticoids. Although the suppression of adrenocortical and pituitary gland functions by glucocorticoids has been shown in humans, a feedback effect at the level of the hypothalamus, as shown in rat, has not been reported to date. The present study shows for the first time that glucocorticoids suppress both CRH and vasopressin (AVP) in the human hypothalamus. We studied immunocytochemically the postmortem hypothalami of nine corticosteroid-exposed subjects and eight controls. The number of CRH-expressing cells in the hypothalamic paraventricular nucleus of glucocorticoid-exposed patients was only 3.3% of that in the controls, and the total immunoreactivities for AVP were 31% and 33% of that in the controls in the supraoptic nucleus and the paraventricular nucleus, respectively, whereas the immunoreactivity for oxytocin did not differ between the two groups. Suppression of hypothalamic CRH and AVP neurons by glucocorticoids may have important consequences for neuroendocrinological mechanisms such as the disturbance of water balance during the treatment as well as the immunological processes in the brain and the pathogenesis of the withdrawal syndrome after discontinuation of corticosteroid treatment. In addition, as both AVP and CRH neurons also project to other brain structures and influence memory, mood, and behavior, their suppression by glucocorticoids may be responsible for at least part of the central nervous system side-effects of glucocorticoids.
TL;DR: Body weight and daily consumption of food and water were not altered, but social isolation caused a reduction in plasma corticosterone levels, both under basal and stress-stimulated con...
Abstract: We have studied the effects of long-term social isolation of male Wistar rats, after early weaning (16 days), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis. In addition to studying basal HPA activity, the response of the HPA axis to 15 min of immobilization stress was examined. Plasma corticosterone concentrations were measured, and the relative weights of adrenal glands, thymus, and testes were obtained, the latter to check whether gonadal function was affected by the isolation paradigm. Moreover, we carried out a quantitative immunohistochemical study of pituitary ACTH and its hypothalamic secretagogues: CRF, arginine vasopressin (AVP), and oxytocin (OT), both at the level of the synthesizing cell bodies in the hypothalamic paraventricular nucleus and of the releasing fibers in the median eminence (ME). Body weight and daily consumption of food and water were not altered, but social isolation caused a reduction in plasma corticosterone levels, both under basal and stress-stimulated conditions; this was correlated with an increased thymus weight, without affecting adrenal or testicular weights. The immunohistochemical study revealed that isolation caused a smaller increase in the number of ACTH-immunoreactive cells in the pars distalis of the anterior pituitary after exposure to restraint stress, as compared with control animals. This result indicates that fewer corticotrophs were activated by restraint stress in isolated animals, such cells being smaller and exhibiting a smaller ACTH-immunoreactive area than in control animals. Isolated animals also showed an increase in the content of CRF-ir fibers in the ME and a smaller decrease in the neuropeptide immunoreactivity after stress than that observed in control animals. This result could indicate a reduced release of CRF into the portal vasculature in response to acute stress and may partially explain the reduced activation of corticotrophs observed in the pituitary of isolated animals. However, no changes were found in the content of CRF, AVP, or OT within the paraventricular nucleus, nor of the AVP or OT content in the ME. The results of this study show that long-term social isolation after early weaning caused a hypofunction of the HPA axis in the adult rat. This hypofunction was particularly evident after exposure to an acute stressor, suggesting a desensitization of this axis to stressful stimuli.
TL;DR: It is concluded that central projections of the PVN modulate maternal aggression during a restricted period after delivery, only when lactating females show naturally high levels of aggressive behaviors.
TL;DR: The results reveal that OT neurons are part of a hypothalamic rhythmic network in which a glutamatergic input governs burst generation, and OT neurons exert a positive feedback on their afferent drive through the release of OT.
Abstract: During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bursting electrical activity responsible for pulsatile OT release. We investigated this activity using hypothalamic organotypic slice cultures enriched in magnocellular OT neurons. As shown here, the neurons are functional and actively secrete amidated OT into the cultures. Intracellular recordings were made from 23 spontaneously bursting and 28 slow irregular neurons, all identified as oxytocinergic with biocytin and immunocytochemistry. The bursting electrical activity was similar to that described in vivo and was characterized by bursts of action potentials (20.1 ± 4.3 Hz) lasting ∼6 sec, over an irregular background activity. OT (0.1–1 μm), added to the medium, increased burst frequency, reducing interburst intervals by 70%. The peptide also triggered bursting in 27% of nonbursting neurons. These effects were mimicked by the oxytocin receptor (OTR) agonist [Thr4, Gly7]-OT and inhibited by the OTR antagonist desGly-NH2d(CH2)5[d-Tyr2,Thr4]OVT. Burst rhythmicity was independent of membrane potential. Hyperpolarization of the cells unmasked volleys of afferent EPSPs underlying the bursts, which were blocked by CNQX, an AMPA/kainate receptor antagonist. Our results reveal that OT neurons are part of a hypothalamic rhythmic network in which a glutamatergic input governs burst generation. OT neurons, in turn, exert a positive feedback on their afferent drive through the release of OT.
TL;DR: The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion.
Abstract: Uterine peristalsis, directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Chlomiphene tended, though insignificantly so, to suppress the frequency of peristaltic waves in the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system.
TL;DR: Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour, and it is speculated that this decrease in OTR mRNA represents in-vivo OTR desensitization.
Abstract: sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR
TL;DR: The results show that endogenous opioid inhibition emerges in pregnancy to restrict the responses of oxytocin neurones to a stressor, and the endogenous opioid enhancement of mechanisms regulating HPA axis secretory responses in virgin rats is not evident during pregnancy.
Abstract: Endogenous opioid regulation of neurohypophysial and hypothalamo-pituitary-adrenal (HPA) axis hormone secretion in response to forced swimming (90 s in deep water at 19 degrees C) was investigated in virgin and 21-day-pregnant rats. There was no difference in basal plasma oxytocin concentrations between pregnant and virgin rats, but the opioid antagonist, naloxone, increased basal oxytocin secretion in the pregnant rats. Forced swimming increased oxytocin secretion similarly in pregnant and virgin rats, and this response was enhanced by naloxone. In pregnant rats naloxone had a greater effect (by 3.1-fold) than in virgins, showing stronger endogenous opioid restraint of an enhanced oxytocin secretory response to stress in pregnancy. Vasopressin secretion was not increased with forced swimming in virgin or pregnant rats, and naloxone had no effect. ACTH and corticosterone secretion in response to forced swimming was attenuated in pregnant rats compared to virgin rats, measured at 5 min. Naloxone had no effect on basal plasma ACTH or corticosterone concentration, but it reduced ACTH secretion in virgin rats 5 min after forced swimming; in pregnant rats naloxone had no such effect. Naloxone removed the pregnancy-related attenuation in corticosterone secretion measured at 5 min after forced swimming. Fifteen minutes after forced swimming, plasma corticosterone concentrations were not different between groups. In the late-pregnant rats, the increases in plasma ACTH and corticosterone induced by forced swimming were significantly prolonged compared to virgins. The results show that endogenous opioid inhibition emerges in pregnancy to restrict the responses of oxytocin neurones to a stressor. In contrast, the endogenous opioid enhancement of mechanisms regulating HPA axis secretory responses in virgin rats is not evident during pregnancy.
TL;DR: It is shown that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.
Abstract: The aim of the present study was to investigate possible long-term effects of postnatally administered oxytocin on weight gain, gastrointestinal hormone levels, and nociceptive thresholds in rats. For this purpose, s.c. daily injections of oxytocin (1 mg/kg) or saline (NaCl, 0.9%) were given to male and female rat pups on d 10-14 after birth. The animals were killed at the age of 60 or 94 d. Treatment with oxytocin resulted in higher body weight in males, 60 d after birth, and in females from d 60 and throughout the rest of the experiment, compared with controls. The higher body weight was due to an increased weight gain in oxytocin-treated rats, compared with controls, which was most pronounced between 40 and 60 d after birth. Oxytocin-treated male rats had increased circulating levels of cholecystokinin, a tendency to increased plasma levels of insulin (p = 0.066), and relatively more adipose tissue in the thigh and interscapular region, compared with controls. At the age of 60 d, oxytocin-treated female and male rats had a prolonged withdrawal latency when measured in the tail-flick test, compared with controls. This study shows that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.