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

It has been postulated that intrauterine volume plays a role in the timing of parturition. In previous studies we found that the onset of parturition in the rat was associated with marked increases in the concentrations of receptors for estrogen and oxytocin in the myometrium. To determine the effects of intrauterine volume on the concentrations of these myometrial receptors, we compared receptor levels in gravid and nongravid uterine horns from unilaterally pregnant rats at or near the time of parturition. Myometria from gravid horns contained substantially greater concentrations of DNA and protein per horn than did myometria from the contralateral nongravid horns. The amounts of receptors per horn for estrogen in the nuclear and cytosol fractions and for oxytocin were 7.5, 5.2, and 4.5 times greater, respectively, in myometria from gravid horns. However, the concentration of receptors per cell was the same in gravid and nongravid horns at or near parturition. These results suggest that uterine stretch causes hyperplasia and hypertrophy of the myometrium, indicative of more DNA and protein per gravid horn than nongravid horn. The sharp rise in concentration per cell of receptors for estrogen and oxytocin occurring about the time of labor, however, appears to be induced by hormonal and not physical factors.
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PMID:Oxytocin receptors and parturition. II. Concentrations of receptors for oxytocin and estrogen in the gravid and nongravid uterus at term. 624 48

Rats were made unilaterally pregnant by tying the right oviduct on the day after mating, to compare the oxytocin receptor concentrations in a nondistended, nonpregnant uterine horn with those in a distended, pregnant horn. On day 20, they were subjected to bilateral ovariectomy and indwelling balloons were inserted into both uterine horns. Following ovariectomy, the rats were injected im with either oil, estradiol benzoate (5 micrograms/rat per 24 h), or estradiol and progesterone together. For comparison, intact rats were studied on days 21 and 22, 24 and 48 h after insertion of the indwelling balloons. Spontaneous uterine activity and the response to increasing amounts of oxytocin were recorded 20-24 h and 44-48 h after surgery, following which the uteri were excised and assayed for oxytocin and estrogen receptors. The oxytocin receptor concentrations in the two horns were different on day 20 before the treatments were begun, the distended pregnant horn having a higher concentration per milligram DNA than the nonpregnant horn. The various treatments always changed the oxytocin receptor concentrations in the same direction; estrogen increased and progesterone inhibited the estrogen-induced rise in oxytocin receptor concentrations. In intact rats, the distention-induced increase in oxytocin receptor concentrations present on day 20 disappeared near term, but in the absence of the ovaries distention of the uterus had a significant influence on the myometrial oxytocin receptor concentrations, potentiating the effect of estrogen. Progesterone selectively inhibited the distention-induced increase in oxytocin receptor concentrations without inhibiting the hypertrophic effect of distention in general. A good correlation between oxytocin receptor numbers and tissue responsiveness was observed in all instances. The changes in spontaneous activity induced by the various treatments were distinct from the changes in oxytocin responsiveness. Estrogen exerted a strong inhibitory action on the activity stimulated by hormone withdrawal, while progesterone had no inhibitory effect. The pregnant distended horn always showed more spontaneous activity than the nonpregnant horn. There was an overall significant correlation between nuclear estrogen receptor and oxytocin receptor concentrations per milligram DNA, although the partial correlations were not significant in all groups (oil and progesterone).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic and local regulation of oxytocin receptors in the rat uterus, and their functional significance. 631 57

Partially purified cell membranes were prepared from midterm and term placentas after sedimentation on a sucrose density gradient. Biochemical characterization showed that the sucrose density pellet was enriched 8-fold in alkaline phosphatase activity and also contained the majority of [125I]LHRH binding sites. This enrichment was also confirmed by electron microscopy. Specific binding of LHRH was then determined by incubating iodinated LHRH or two of its superanalogs with increasing doses of the corresponding radioinert ligand. Scatchard representation of the data showed curvilinear plots whose first component revealed, for both stages of pregnancy, saturable binding of [125I]LHRH and its agonists with similar association constants (Ka) that ranged between 5.5 X 10(5) M-1 and 1.1 X 10(7) M-1. When standardized per milligram of DNA content, the number of binding sites ranged between 225 and 310 X 10(-12) M. Specificity was evidenced by the inability of a biologically active LHRH antagonist, oxytocin, and TRH to inhibit [125I]LHRH binding. Short term placental cultures incubated with 1.5 X 10(-6)M LHRH had increased production rates of both immunoassayable and bioassayable hCG, and this effect was 4-fold higher in midterm placental cultures. Placental incubations with either buffer or equimolar concentrations of oxytocin or TRH had no effect on hCG production. These observations expand information on extrapituitary binding sites of LHRH and suggest a role for this peptide in the physiology of the human placenta.
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PMID:Luteinizing hormone-releasing hormone binds to enriched human placental membranes and stimulates in vitro the synthesis of bioactive human chorionic gonadotropin. 632 54

The neurophysin that is biosynthesised in association with the neurohypophysial hormone vasopressin (vasopressin-neurophysin) affects the growth and DNA synthesis of rat hypothalamic non-neuronal cells in culture. Over a narrow range of concentrations vasopressin-neurophysin stimulated growth, as assessed by increase in cell numbers, about five-fold, in conditions where fetal calf serum concentration was limiting (0.2% fetal calf serum). Maximum stimulation occurred in the presence of 20 to 30 ng vasopressin-neurophysin per ml of medium. DNA synthesis was increased by a factor of three in the presence of 30 ng vasopressin-neurophysin per ml of medium. At least two populations of non-neuronal hypothalamic cells were present in the cultures, and these were both affected by vasopressin-neurophysin. This study allows the suggestion that neurophysin may be acting as a growth-regulating factor at its release site, playing a part in the interactions of neurones and glial cells in the hypothalamo-neurohypophysial system.
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PMID:Non-neuronal cells of rat hypothalamus in dissociated cell culture. Evidence that neurophysin modulates growth and DNA synthesis of non-neuronal cells. 647 78

Using a combination of in vitro methodology, including cell-free translation, two-dimensional peptide mapping and recombinant DNA techniques, the structure of the precursors of the hypothalamic nonapeptide hormones vasopressin and oxytocin has been elucidated. Both hormone precursors are model cellular polyproteins in that they comprise several different entities within the same polypeptide molecule. In each precursor, the nonapeptide hormone follows immediately the signal peptide and is, in turn, attached to its respective carrier neurophysin. The vasopressin precursor also includes a pituitary glycoprotein at its C-terminus. The posttranslational processing of the precursors to set free the nonapeptide hormones is thus a critical regulatory step, which can in part be simulated in the quasi in vivo system of the Xenopus laevis oocyte. The preprohormones to vasopressin and oxytocin illustrate well the convenience of the in vitro experimental approach in understanding the function of the peptidergic neuron.
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PMID:Vasopressin and oxytocin precursors as model preprohormones. 662 4

Prostaglandins (PGs) are thought to have an important function in the initiation and/or propagation of parturition. To define the relationship of individual PGs to one another and compare their alterations with gestational age, PGF, PGE, 6-keto-PGF1 alpha (6KF) and thromboxane B2 (TxB2) were measured in uterine and placental tissue and uterine venous plasma of rats at Days 15, 18, 19, 20, and 21 of pregnancy and at delivery (Day 21 1/2). In addition, concomitant measurements of peripheral plasma estradiol (E2), estrone (E1) and progesterone (P) and pituitary oxytocin (OT) content, putative regulators and/or modulators of PG metabolism, were determined. Significant enhancements (P less than 0.05) in uterine 6KF, TxB2, PGF and PGE concentrations (ng/mg DNA) were detected by Day 20 compared to Day 15 of pregnancy and further dramatic increases were found on Day 21 and at delivery. Although uterine 6KF was present in the highest concentrations, PGF showed the greatest increment from Day 15 to delivery. No alterations in uterine venous plasma PGE or PGF concentration were found with gestational age but 6KF and TxB2 showed significant increases at delivery. The placental concentrations of PGs were approximately 1/50 of uterine tissue. Placental PGE and PGF concentrations (ng/mg DNA) increased only slightly at delivery but the augmentation in 6KF and TxB2 levels were of greater magnitude. Significant increases in E2 and E1 with reciprocal decreases in P occurred on Day 21 of pregnancy. In contrast, pituitary OT content showed no alterations at any of the days examined. These results are consonant with the hypothesis that uterine PGs have an important function in parturition and uterine-placental physiology, and suggest that an increasing estrogen/P ratio at the end of pregnancy is related to enhanced uterine PG levels.
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PMID:Alterations in reproductive tissue prostaglandins E and F, 6-keto-prostaglandin F1 alpha and thromboxane B2 with gestational age in the rat. 689 17

The novel nucleoside oxetanocin G, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine (OXT-G), that is a derivative of oxetanocin A, was studied in relation to its action on the synthesis of hepatitis B virus (HBV) DNA and cellular DNA in an HBV-producing cell line, HB611 (T. Tsurimoto, A. Fujiyama, and K. Matsubara, Proc. Natl. Acad. Sci. USA 84:444-448, 1987). The median effective concentration of OXT-G against HBV replication was 1.5 microM, and the median cytotoxic concentration was more than 1,000 microM. At the same concentration, OXT-G did not inhibit cellular DNA synthesis or viral RNA synthesis. Chemically synthesized OXT-GTP inhibited the HBV endogenous DNA polymerase reaction and was incorporated into HBV DNA strands at a low efficiency compared with the incorporation of dGTP. A synthetic primer-template study revealed that OXT-GTP was incorporated into DNA strands at a low efficiency and that further extension of the DNA strand by using the 2' position of the incorporated OXT-G could take place.
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PMID:Effect of oxetanocin G, a novel nucleoside analog, on DNA synthesis by hepatitis B virus virions. 751 17

The neurohypophysial endocrine regulatory cascade has been described as a molecular model of neuroendocrine control of organismal functions. Any physiological function can be analyzed in molecular terms as a succession of interactions occurring either in a solution or in a membrane system. The key mechanism in the ordering of the cascade is the conformational recognition of the two partners at each step. Each interaction results in a change of conformation of a recognized protein that in turn becomes a recognizer for the following molecule. The cascade starts within the secretory cell by the processing of the expressed precursor along the secretory pathway until the storage of the mature mediator in vesicles and its subsequent exocytic secretion in blood. The circulating mediator recognizes the target cell through specific membrane receptors that transduce the message within this target cell. A second intracellular cascade leads to activation of the effector, the protein fulfilling the physiological function. The complexity of the messages is, in part, due to the duplication propensity of the genomic DNA, the frequent occurrence of multiple copies for precursors, mediators, receptors, and effectors, and therefore, a combinatorial diversity that increases during the course of evolution. Vertebrate neurohypophysial hormones can be ordered in two main evolutionary lineages, culminating in oxytocin and vasopressin in placental mammals. In this field, diversification of the messages was made by differential processing of the precursors, secondary gene duplications, the emergence of several types of receptors for each hormone, and a variety of effectors triggered by the second messengers within differentiated target cells. This review is an attempt to integrate neurohypophysial functions at the molecular, cellular, and organismal levels.
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PMID:The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors, and effectors. 755 52

S-(2-Chloroethyl)glutathione (CEG), an alkylating agent formed by glutathione conjugation with 1,2-dichloroethane (DCE), is able to alkylate DNA and proteins. As a prelude to identification of specific protein alkylation sites, the peptide oxytocin was alkylated by CEG, and tandem mass spectrometry was used to identify the alkylation sites. It was found that mono-, bis-, and tris-adducts can result from alkylation of reduced oxytocin and that tandem mass spectrometry differentiated (S-[2-(Cys1)ethyl]glutathione)oxytocin (mono-adduct Cys-1) from (S-[2-(Cys1,6)ethyl]glutathione)oxytocin (mono-adduct Cys-6). Manual Edman degradation was used to eliminate the possibility that alkylation has occurred at Tyr-2 rather than at Cys-1 in the case of (S-[2-(Cys1,6)ethyl]glutathione)oxytocin (bis-adduct) and mono-adduct Cys-1. A mono-adduct homodimer resulting from alkylation at Cys-6 and disulfide bridge formation through Cys-1 was also identified. Oxidized oxytocin formed two minor adducts, representing less than 5% of the oxytocin present in the reaction mixture. These findings demonstrate that alkylation of oxytocin by the episulfonium ion of CEG did occur, as evidenced by tandem mass spectrometry, and that characterization of these adducts will aid in the identification of alkylated amino acids in proteins exposed to CEG.
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PMID:Alkylation of oxytocin by S-(2-chloroethyl)glutathione and characterization of adducts by tandem mass spectrometry and Edman degradation. 757 28

To gain insights into the molecular mechanisms that restrict the expression of the oxytocin gene to anatomically defined groups of neurons in the hypothalamus, we generated transgenic mice bearing bovine oxytocin genomic fragments. Appropriate neuron-specific and physiological regulation was observed in mice bearing transgene bOT3.5, which consists of the oxytocin structural gene flanked by 0.6 kilobase pair (kbp) of upstream and 1.9 kbp of downstream sequences. bOT3.5 is expressed in oxytocin magnocellular neurons in the mouse supraoptic nucleus and paraventricular nucleus, but transgene RNAs are excluded from vasopressin neurons. Replacement of the drinking diet of the transgenic mice with 2% (w/v) NaCl for 7 days significantly increased the abundance of bovine oxytocin transcripts in the supraoptic nucleus, but not in the paraventricular nucleus, in parallel with the endogenous mouse oxytocin RNA. Surprisingly, mimicry of the endogenous oxytocin gene expression pattern was lost with larger transgenes. Addition of 0.7 kbp of contiguous downstream sequences (transgene bOT) or linkage to the bovine vasopressin gene (transgene VP-B/bOT3.5) repressed hypothalamic expression. No mice were derived bearing transgene bOT6.4, which consists of the oxytocin structural gene flanked by 3 kbp of upstream and 2.6 kbp of downstream sequences, suggesting that the presence of this DNA is detrimental to normal embryonic development. These data suggest that while bOT3.5 contains sufficient cis-acting sequences to mediate expression to particular subsets of hypothalamic neurons, the overall regulation of the oxytocin gene is governed by multiple interacting enhancers and repressors.
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PMID:Bovine oxytocin transgenes in mice. Hypothalamic expression, physiological regulation, and interactions with the vasopressin gene. 759 77


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