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Actions of parathyroid hormone, parathyroid hormone-related peptide and calcitonin gene-related peptide in the fetal-placental circulation
A.48
Placenta (1993), Vol 14
ACTIONS OF PARATHYROID HORMONE, PARATHYROID HORMONE-RELATED PEPTIDE AND CALCITONIN GENE-RELATED PEPTIDE IN THE FETALPLACENTAL CIRCULATION. NT Mandsager, A Brewer and L Myatt. Dept Ob/Gyn, University of Cincinnati College of Medicine, Cincinnati, OH 45267 USA. Parathyroid hormone (PTH), parathyroid hormone-related peptida (PTHrp) and calcitonin gene-related peptide (CGRP) are vasodilators in various human tissues and have been localized in the uteroplacental complex. We have determined the vasoactlve effects of PTH, PTHrp and CGRP in the isolated perfused cotyledon from normotensive term human placentae. In each experiment the fetal-placental circulation was preconstricted with a constant infusion of thromboxane mimetic U46619 (lO-ZM). Increasing concentrations of PTH (lO'a-lOeM, n=5), PTHrp (10"l~ n=4) or CGRP (101~ n=6) were then infused in a cumulative fashion and changes with perfusion pressure recorded. All three peptides gave a concentration-dependent vasodilator effect (p=O.O02, p=0.015, p=O.O02 for PTH, PTHrp and CGRP respectively, one way ANOVA). Perfusion pressure was reduced by approximately 50% at the highest concentration of each poptide. PTHrp and CGRP were oquipotent, but approximately 100 times more potent than PTH. The CGRP receptor-1 antagonist CGRP~7 (106M) only partially antagonized (70%) the effect of CGRP suggesting a second receptor subtype may also mediate CGRP-induced vasodilation. The nitric oxide synthase inhibitor n-nitro L-arginine (104M) did not affect the response to CGRP suggesting nitric oxide does not mediate the effect of CGRP. We conclude that the peptides PTH, PTHrp and CGRP may therefore act as vasodilators in the human fetal-placental circulation.
OVEREXPRESSION OF p53 PROTEIN IN HUMAN TROPHOBLAST. K. Marzusch ~ , P. Ruck 2, H.-P. Horny = J. Dietl I, E. Kaiserling =, Department of Obstetrics and Gynecology ~ and Institute of Pathology =, University of T~bingen, Germany. Immunohistochemically detectable overexpression of p53 protein is found in many different malignant tumors. Since human trophoblast undergoes extensive proliferation and its invasive growth is comparable to that of a malignant tumor, human tropboblast at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumor suppressor gene. Overexpression of p53 protein was found in the nuclei of a small number of trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all the specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased overexpression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of epidermal growth factor receptor have been described. It is probable that overexpression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumors, but rather to upregulation of the p53 tumor suppressor gene, which could be a mechanism for controlling trophoblast proliferation.
Placenta (1993), Vol 14
ACTIONS OF PARATHYROID HORMONE, PARATHYROID HORMONE-RELATED PEPTIDE AND CALCITONIN GENE-RELATED PEPTIDE IN THE FETALPLACENTAL CIRCULATION. NT Mandsager, A Brewer and L Myatt. Dept Ob/Gyn, University of Cincinnati College of Medicine, Cincinnati, OH 45267 USA. Parathyroid hormone (PTH), parathyroid hormone-related peptida (PTHrp) and calcitonin gene-related peptide (CGRP) are vasodilators in various human tissues and have been localized in the uteroplacental complex. We have determined the vasoactlve effects of PTH, PTHrp and CGRP in the isolated perfused cotyledon from normotensive term human placentae. In each experiment the fetal-placental circulation was preconstricted with a constant infusion of thromboxane mimetic U46619 (lO-ZM). Increasing concentrations of PTH (lO'a-lOeM, n=5), PTHrp (10"l~ n=4) or CGRP (101~ n=6) were then infused in a cumulative fashion and changes with perfusion pressure recorded. All three peptides gave a concentration-dependent vasodilator effect (p=O.O02, p=0.015, p=O.O02 for PTH, PTHrp and CGRP respectively, one way ANOVA). Perfusion pressure was reduced by approximately 50% at the highest concentration of each poptide. PTHrp and CGRP were oquipotent, but approximately 100 times more potent than PTH. The CGRP receptor-1 antagonist CGRP~7 (106M) only partially antagonized (70%) the effect of CGRP suggesting a second receptor subtype may also mediate CGRP-induced vasodilation. The nitric oxide synthase inhibitor n-nitro L-arginine (104M) did not affect the response to CGRP suggesting nitric oxide does not mediate the effect of CGRP. We conclude that the peptides PTH, PTHrp and CGRP may therefore act as vasodilators in the human fetal-placental circulation.
OVEREXPRESSION OF p53 PROTEIN IN HUMAN TROPHOBLAST. K. Marzusch ~ , P. Ruck 2, H.-P. Horny = J. Dietl I, E. Kaiserling =, Department of Obstetrics and Gynecology ~ and Institute of Pathology =, University of T~bingen, Germany. Immunohistochemically detectable overexpression of p53 protein is found in many different malignant tumors. Since human trophoblast undergoes extensive proliferation and its invasive growth is comparable to that of a malignant tumor, human tropboblast at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumor suppressor gene. Overexpression of p53 protein was found in the nuclei of a small number of trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all the specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased overexpression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of epidermal growth factor receptor have been described. It is probable that overexpression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumors, but rather to upregulation of the p53 tumor suppressor gene, which could be a mechanism for controlling trophoblast proliferation.