UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The various hypothalamic nuclei show very different patterns of change in ageing. These patterns are a basis for changes in biological rhythms, hormones, autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates circadian and circannual rhythms. A marked seasonal and circadian variation in the vasopressin (AVP) cell number of the SCN was observed in relation to the variation in photoperiod. During normal ageing, the circadian variation and number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in adult women. In girls, the SDN shows a first period of decreasing cell numbers during prepubertal development, leading to sexual dimorphism. During ageing a decrease in cell number is found in both sexes. The cells of the supraoptic nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These nuclei are examples of neuron populations that seem to stay perfectly intact in ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons are found throughout the PVN. CRH neurons in the PVN are activated in the course of ageing, as indicated by their increase in number and AVP coexpression. Part of the infundibular (or arcuate) nucleus, the subventricular nucleus, contains hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The NKB neurons may also be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis might be involved in feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ageing of the human hypothalamus. 772 Dec 67

The distribution of gonadotropin-releasing hormone (GnRH)-immunoreactive (ir) cells in the preoptic area (POA) of the dwarf gourami, Colisa lalia, was immunohistochemically studied. These neurons form cell columns on both sides of the common ventricle, and their axons project to the pituitary gland by forming distinct bundles. Also examined was the distribution of isotocin (IST) cells in the POA by using an anti-oxytocin (OXT) serum which has been proven to crossreact with IST. These two kinds of immunoreactive cells were distributed quite similarly in the POA. However, by using an immunofluorescence double-labeling method on thinner sections we found that a population of small IST cells in the ventral POA were also immunoreactive to GnRH, but that large IST cells in the dorsal POA were not immunoreactive to GnRH, and small GnRH-ir cells in the most ventral POA were not immunoreactive to the OXT antiserum. In the pituitary gland, GnRH-ir fibers were found in both the neurohypophysis and proximal pars distalis, but IST fibers were found only in the neurohypophysis.
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PMID:Immunohistochemical double-labeling study of gonadotropin-releasing hormone (GnRH)-immunoreactive cells and oxytocin-immunoreactive cells in the preoptic area of the dwarf gourami, Colisa lalia. 780 2

Fertility management is a global issue of agricultural, medical, economic, and social consequence. Although many methods have been devised to both inhibit and assist reproduction, more acceptable alternatives are needed. Regulation by immune intervention is a promising technology as applied to livestock, pets, wildlife, and human beings. Outcome is dictated by site within the reproductive axis that is targeted. Fertility is suppressed by immunization against gonadotropin-releasing hormone, gonadotropins, prostaglandin F2 alpha, oxytocin, gonadotropin receptors, and gamete/embryonic antigens. It also is possible to lyse gonadal cells with ligand-antibody hybrid molecules. Ovulation rates are enhanced by vaccination with inhibin. Antibodies to sex steroid hormones have yielded mixed results. Perhaps recombinant viral vectors can be used to deliver reproductive immunogens. A new and simple technique to generate sustained autoimmune reactions to hormones and cellular antigens entails direct gene transfer into somatic cells. Evolving advances in reproductive immunology and biotechnology should furnish us with novel nonsurgical contraceptives and profertility agents that can be efficiently and safely implemented.
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PMID:Immunoregulation of mammalian fertility. 799 Jun 47

Recently, specific binding sites for luteinizing hormone releasing hormone (LHRH) and its analogues have been demonstrated in biopsy samples of human epithelial ovarian cancer. Their biological significance remained obscure. In this study we ascertained whether such LHRH-binding sites are also present in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27 and if they could mediate antiproliferative effects of LHRH analogues. Using [125I, D-Trp6]LHRH, a high affinity/low capacity binding site was detected in both lines: EFO-21 (Kd1 = 1.5 x 10(-9) M; binding capacity (Bmax1) = 4.9 fmol/10(6) cells) and EFO-27 (Kd1 = 1.7 x 10(-9) M; Bmax1 = 3 fmol/10(6) cells). In addition, a second class of low affinity/high capacity binding sites (EFO-21: Kd2 = 7.5 x 10(-6) M; Bmax2 = 24 pmol/10(6) cells; EFO-27: Kd2 = 4.3 x 10(-6) M; Bmax2 = 14.5 pmol/10(6) cells) was demonstrated. Specific binding of [125I, D-Trp6]LHRH was displaced with nearly equal efficiency by unlabeled [D-Trp6]LHRH, the LHRH-antagonists SB-75 and Hoe-013, and by native LHRH but not by unrelated peptides such as oxytocin and somatostatin. In the presence of 10(-5) M agonist [D-Trp6]LHRH, the proliferation of both cell lines was significantly reduced to 77% of controls after 24 h and to approx. 60% after 6 days. Lower concentrations (10(-9) M) of the agonist, significantly decreased the proliferation to 87.5% for EFO-21 and 86% for EFO-27 after 6 days. These antiproliferative effects were enhanced by increasing doses of [D-Trp6]LHRH and were maximal at 10(-5) M (EFO-21: 65.5% of control, EFO-27: 68% of control). Similar dose-dependent antiproliferative effects were obtained in EFO-21 line with the LHRH-antagonists SB-75 and Hoe-013, while these analogues had no effects on the proliferation of EFO-27 cells. SB-75 partly antagonized the antiproliferative effect of [D-Trp6]LHRH in a dose dependent way in the EFO-27 line. These data suggest that LHRH analogues can directly inhibit the in vitro proliferation of human ovarian cancer cells. This effect might be mediated through the high affinity LHRH binding sites.
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PMID:High affinity binding and direct antiproliferative effects of LHRH analogues in human ovarian cancer cell lines. 822 83

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

In previous studies, tissue inhibitor of metalloproteinases (TIMP)-1 mRNA increased in follicular tissue after the preovulatory gonadotropin surge and was expressed in luteal tissue. However, the localization of TIMP-1 protein within ovine periovulatory follicular and luteal tissues is unknown. The objectives of the present study were to 1) localize TIMP-1 within follicles collected before and after a preovulatory gonadotropin surge and within Day 3 and Day 10 corpora lutea (CL), 2) determine whether TIMP-1 was colocalized to Day 10 luteal cells with oxytocin or TIMP-2, and 3) determine whether TIMP-1 was present within secretory granules of large luteal cells. Ovaries were removed from ewes before (presurge; n = 4) or 12-14 h after (postsurge; n = 5) an LHRH-induced gonadotropin surge (36 h following PGF2 alpha-induced luteolysis; objective 1). Additionally, ovaries containing CL were collected on Days 3 (n = 5; objective 1) and 10 (n = 4, 3, and 2 for objectives 1, 2, and 3, respectively). TIMP-1 immunoreactivity was observed within the granulosa cells of postsurge but not presurge follicles. On Days 3 and 10, TIMP-1 was localized within luteal tissue in a cell-specific manner. On Day 10, many of the cells that were immunopositive for TIMP-1 were judged to be large luteal cells on the basis of morphology (diameter > 22 microns; round nucleus) and colocalization with oxytocin and TIMP-2. Electron microscopy demonstrated that TIMP-1 was localized to secretory granules undergoing exocytosis from Day 10 large luteal cells. These data indicate that TIMP-1 is produced by granulosa cells following a gonadotropin surge and is packaged in secretory granules by large steroidogenic cells of the ovine CL.
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PMID:Immunolocalization of tissue inhibitor of metalloproteinases-1 within ovine periovulatory follicular and luteal tissues. 892 8

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
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PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

Neurons which release atrial natriuretic peptide (ANPergic neurons) have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V) region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stress-induced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V) injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume.
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PMID:Neuroendocrine regulation of salt and water metabolism. 925 61

The various cell groups in the human hypothalamus show different patterns of aging, which are the basis for changes in biological rhythms, hormone production, autonomic functions, and behavior. The suprachiasmatic nucleus (SCN), the clock of the brain, exhibits circadian and seasonal rhythms in vasopressin synthesis that are disrupted later in life. Furthermore, the age-related sexual differences in the number of vasoactive intestinal polypeptide neurons in this nucleus reinforces the idea that the SCN is not only involved in the timing of circadian rhythms but also in the temporal organization of reproductive functions. The sexually dimorphic nucleus of the preoptic are (SDN-POA), or intermediate nucleus, is twice as large in men as in women, a difference that arises between the ages of two to four years and puberty. During aging a dramatic, sex-dependent decrease in cell number occurs, leading to values which are only 10-15% of the cell number found in early childhood. The vasopressin and oxytocin producing cells in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are examples of neuron populations that seem to stay perfectly intact in old age. Parvocellular corticotropin-releasing hormone-containing neurons are found throughout the PVN and are even activated in the course of aging, as indicated by their increase in number and by their coexpression with vasopressin. Part of the arcuate nucleus of the hypothalamus (ARH), or tubero-infundibular nucleus, contains hypertrophic neurons in postmenopausal women. These hypertrophied neurons contain neurokinin-B, substance P, and estrogen receptors and probably act on LHRH neurons as interneurons. The tuberal lateral nucleus (NTL), involved in feeding behavior and energy metabolism, does not show any neuronal loss in senescence. These findings indicate that each cell group of the human hypothalamus has its own sex-specific pattern of aging. In fact, some hypothalamic nuclei show a dramatic functional decline with aging, whereas others seem to become more active later in life.
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PMID:Lifespan changes in the human hypothalamus. 931 57

1. Studies of the regulation of neurosecretory cell gene expression suffer from the lack of suitable cell lines. Two approaches have been used to overcome this deficit: transfection of neuropeptide genes into heterologous cell lines and generation of transgenic animals. 2. Studies with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin genes. Although limited in their scope, these studies have contributed greatly to the dissection of basic properties of elements in the vasopressin and oxytocin gene promoters. 3. Transgenic mice, and more recently rats, have been used to elucidate genomic regions governing cell specificity and physiological regulation of neurosecretory gene expression. The genes encoding the neuropeptides vasopressin and oxytocin have been used in many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and physiologically regulated expression of these transgenes has been achieved, demonstrating the action of putative repressor elements and regulation of the expression of one gene by sequences present in the other gene. 4. Appropriate expression and translation of transgenes have resulted in the production of several useful systems. Expression of oncogene sequences in gonadotropin-releasing hormone neurons has allowed the development of cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has generated a potentially useful rat model of dwarfism. These and other animal models of human disease will provide important avenues for the development of therapeutic strategies.
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PMID:Transgenic and transcriptional studies on neurosecretory cell gene expression. 953 88

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