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Laird Wilson - One of the best experts on this subject based on the ideXlab platform.
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hormonal regulation of uterine secretion of Prostaglandin F2 Alpha during luteolysis in ruminants
Biology of Reproduction, 1991Co-Authors: W.j. Silvia, John A. Mccracken, William W. Thatcher, G S Lewis, Laird WilsonAbstract:In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of Prostaglandin F,,, (PGF,,,) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF,,, secretion from the uterus. Uterine PGF,,, stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF,,, from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenom. enon occurs in response to PGF,,, at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF,,, observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous. pulsatile secretion of PGF,,, normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF,,. occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF,,, secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, Prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF,,,.. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF,,, is secreted only at the appropriate time to induce luteolysis. Estradiol has a number of effects that may contribute to the regulation of uterine PGF2,, secretion. It has direct effects on the uterus that maximize its responsiveness to oxytocin and may modulate pulsatile secretion of neurohypophyseal oxytocin. These endocrine interactions result in a characteristic pattern of PGF,,, secretion from the uterus. The first pulses of PGF,,, are relatively low in magnitude. These pulses probably initiate luteal regression. Once luteolysis begins, pulse magnitude increases, perhaps because of changes in concentrations of progesterone and estradiol associated with luteal regression. These high magnitude pulses may complete the luteolytic process.
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hormonal regulation of uterine secretion of Prostaglandin F2 Alpha during luteolysis in ruminants
Biology of Reproduction, 1991Co-Authors: W.j. Silvia, John A. Mccracken, William W. Thatcher, G S Lewis, Laird WilsonAbstract:In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of Prostaglandin F2 Alpha (PGF2 Alpha) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2 Alpha secretion from the uterus. Uterine PGF2 Alpha stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2 Alpha from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2 Alpha at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2 Alpha observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2 Alpha normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2 Alpha occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2 Alpha secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, Prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2 Alpha. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2 Alpha is secreted only at the appropriate time to induce luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
James D Lindsey - One of the best experts on this subject based on the ideXlab platform.
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induction of c fos by Prostaglandin F2 Alpha in human ciliary smooth muscle cells
Investigative Ophthalmology & Visual Science, 1994Co-Authors: James D Lindsey, Robert N WeinrebAbstract:Purpose To evaluate the induction of the proto-oncogene c-fos in cultured human ciliary muscle cells by Prostaglandin F2 Alpha (PGF2 Alpha) by 17-phenyltrinor-PGF 2 Alpha. Method Human ciliary muscle cells were grown to confluency in monolayer cell culture, placed in medium containing 1% fetal bovine serum for 5 days, treated by addition of PGF2 Alpha or the trinor derivative, fixed, and then immunocytochemically stained using an antibody to c-Fos, the protein product of the translation of c-fos. Results After treatment with either agonist, the mean induction score (proportion of brightly immunostained nuclei) increased to a maximal level during the first hour and returned to basal levels 4 to 8 hours after treatment. Increasing the agonist concentration increased the maximal level, but had no effect on the time course of the response. The dose responses after 1 hour of treatment with PGF2 Alpha or 17-phenyltrinor-PGF2 Alpha increased similarly between 1.6 x 10(-9) M and 2 x 10(-7) M. When treated with 1 x 10(-6) M of either agonist, however, the induction was half that obtained at 2 x 10(-7) M. Conclusion Exposure of ciliary smooth muscle cells to either PGF2 Alpha or 17-phenyltrinor-PGF2 Alpha induces an immediate early gene expression response that is similar to c-Fos induction in other cell systems. These results establish the basis for future investigations evaluating the potential role of c-fos induction in mediating the effects of PGF2 Alpha on uveoscleral outflow.
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propagation of ciliary smooth muscle cells in vitro and effects of Prostaglandin F2 Alpha on calcium efflux
Investigative Ophthalmology & Visual Science, 1992Co-Authors: Robert N Weinreb, Dong Myung Kim, James D LindseyAbstract:The effect of Prostaglandin F2 Alpha (PGF2 Alpha) on calcium efflux from ciliary smooth muscle cells was studied. Ciliary smooth muscle cells, cultured from human ciliary muscle explants, retained the morphologic and immunologic characteristics of smooth muscle cells. High concentrations (to 10(-6) mol/l) of PGF2 Alpha were associated with a dose-dependent increase of calcium (45Ca) efflux, whereas at concentrations lower than 10(-8) mol/l there was little or no 45Ca efflux. Our in vitro data are inconsistent with the experimental hypothesis that PGF2 Alpha at pharmacologic concentrations relaxes ciliary muscle with a consequent increase in uveoscleral outflow.
Robert N Weinreb - One of the best experts on this subject based on the ideXlab platform.
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induction of c fos by Prostaglandin F2 Alpha in human ciliary smooth muscle cells
Investigative Ophthalmology & Visual Science, 1994Co-Authors: James D Lindsey, Robert N WeinrebAbstract:Purpose To evaluate the induction of the proto-oncogene c-fos in cultured human ciliary muscle cells by Prostaglandin F2 Alpha (PGF2 Alpha) by 17-phenyltrinor-PGF 2 Alpha. Method Human ciliary muscle cells were grown to confluency in monolayer cell culture, placed in medium containing 1% fetal bovine serum for 5 days, treated by addition of PGF2 Alpha or the trinor derivative, fixed, and then immunocytochemically stained using an antibody to c-Fos, the protein product of the translation of c-fos. Results After treatment with either agonist, the mean induction score (proportion of brightly immunostained nuclei) increased to a maximal level during the first hour and returned to basal levels 4 to 8 hours after treatment. Increasing the agonist concentration increased the maximal level, but had no effect on the time course of the response. The dose responses after 1 hour of treatment with PGF2 Alpha or 17-phenyltrinor-PGF2 Alpha increased similarly between 1.6 x 10(-9) M and 2 x 10(-7) M. When treated with 1 x 10(-6) M of either agonist, however, the induction was half that obtained at 2 x 10(-7) M. Conclusion Exposure of ciliary smooth muscle cells to either PGF2 Alpha or 17-phenyltrinor-PGF2 Alpha induces an immediate early gene expression response that is similar to c-Fos induction in other cell systems. These results establish the basis for future investigations evaluating the potential role of c-fos induction in mediating the effects of PGF2 Alpha on uveoscleral outflow.
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propagation of ciliary smooth muscle cells in vitro and effects of Prostaglandin F2 Alpha on calcium efflux
Investigative Ophthalmology & Visual Science, 1992Co-Authors: Robert N Weinreb, Dong Myung Kim, James D LindseyAbstract:The effect of Prostaglandin F2 Alpha (PGF2 Alpha) on calcium efflux from ciliary smooth muscle cells was studied. Ciliary smooth muscle cells, cultured from human ciliary muscle explants, retained the morphologic and immunologic characteristics of smooth muscle cells. High concentrations (to 10(-6) mol/l) of PGF2 Alpha were associated with a dose-dependent increase of calcium (45Ca) efflux, whereas at concentrations lower than 10(-8) mol/l there was little or no 45Ca efflux. Our in vitro data are inconsistent with the experimental hypothesis that PGF2 Alpha at pharmacologic concentrations relaxes ciliary muscle with a consequent increase in uveoscleral outflow.
W.j. Silvia - One of the best experts on this subject based on the ideXlab platform.
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hormonal regulation of uterine secretion of Prostaglandin F2 Alpha during luteolysis in ruminants
Biology of Reproduction, 1991Co-Authors: W.j. Silvia, John A. Mccracken, William W. Thatcher, G S Lewis, Laird WilsonAbstract:In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of Prostaglandin F,,, (PGF,,,) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF,,, secretion from the uterus. Uterine PGF,,, stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF,,, from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenom. enon occurs in response to PGF,,, at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF,,, observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous. pulsatile secretion of PGF,,, normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF,,. occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF,,, secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, Prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF,,,.. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF,,, is secreted only at the appropriate time to induce luteolysis. Estradiol has a number of effects that may contribute to the regulation of uterine PGF2,, secretion. It has direct effects on the uterus that maximize its responsiveness to oxytocin and may modulate pulsatile secretion of neurohypophyseal oxytocin. These endocrine interactions result in a characteristic pattern of PGF,,, secretion from the uterus. The first pulses of PGF,,, are relatively low in magnitude. These pulses probably initiate luteal regression. Once luteolysis begins, pulse magnitude increases, perhaps because of changes in concentrations of progesterone and estradiol associated with luteal regression. These high magnitude pulses may complete the luteolytic process.
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hormonal regulation of uterine secretion of Prostaglandin F2 Alpha during luteolysis in ruminants
Biology of Reproduction, 1991Co-Authors: W.j. Silvia, John A. Mccracken, William W. Thatcher, G S Lewis, Laird WilsonAbstract:In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of Prostaglandin F2 Alpha (PGF2 Alpha) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2 Alpha secretion from the uterus. Uterine PGF2 Alpha stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2 Alpha from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2 Alpha at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2 Alpha observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2 Alpha normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2 Alpha occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2 Alpha secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, Prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2 Alpha. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2 Alpha is secreted only at the appropriate time to induce luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Garret A Fitzgerald - One of the best experts on this subject based on the ideXlab platform.
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immunological characterization of urinary 8 epi Prostaglandin F2 Alpha excretion in man
Journal of Pharmacology and Experimental Therapeutics, 1995Co-Authors: Zhaoyue Wang, John A Lawson, Garret A Fitzgerald, G Ciabattoni, C Creminon, Carlo Patrono, Jacques MacloufAbstract:F2-isoprostanes are Prostaglandin (PG) F2-like compounds that are formed in vivo directly by free radical-catalyzed lipid peroxidation. One of the compounds that can be produced in abundance by such mechanism is 8-epi-PGF2 Alpha, a potent vasoconstrictor. We have developed an enzyme immunoassay and a radioimmunoassay for measuring urinary concentrations of 8-epi-PGF2 Alpha by raising antibodies against this compound. The antisera presented high titers (> 1/300,000) and provided highly sensitive assays (IC50, 8 and 24 pg/ml, for EIA and RIA, respectively); cross-reactivity with other PG was negligible. The interassay reproducibility of EIA was assessed by measuring the same urine stored frozen in aliquots after solid phase extraction and thin-layer chromatography (17%, n = 13). Measurements of urinary 8-epi-PGF2 Alpha by immunoassays were validated using different antisera and by comparison with gas chromatography/mass spectrometry. Healthy volunteers excreted 25 +/- 12 ng of 8-epi-PGF2 Alpha/mmol creatinine (n = 19), with no circadian variation over three consecutive 8-hr collection periods (n = 10); preliminary results showed that excretion increased as a function of age. Urinary excretion of 8-epi-PGF2 Alpha was unchanged by treatment with two nonsteroidal antiinflammatory drugs, Ibuprofen at 1.2 g/day for 4 days (n = 4) or aspirin as a single administration of 1 g (n = 6). In contrast, the urinary excretion of 11-dehydro-thromboxane B2, a platelet cyclooxygenase-derived metabolite was reduced by more than 80% after aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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cyclooxygenase dependent formation of the isoprostane 8 epi Prostaglandin F2 Alpha
Journal of Biological Chemistry, 1995Co-Authors: Domenico Pratico, John A Lawson, Garret A FitzgeraldAbstract:Isoprostanes are a family of Prostaglandin (PG) isomers formed in an enzyme-independent manner. They circulate in plasma and are excreted in urine. One of them, 8-epi PGF2 Alpha is a vasoconstrictor and mitogen, effects which are prevented by thromboxane antagonists. Given that 8-epi PGF2 Alpha may be formed by cyclooxygenase (COX) (Corey, E. J., Shih, C., Shig, N-Y., and Shimoji, K. (1984) Tetrahedron Letts. 44, 5013-5016; Hecker, M., Ullrich, V., Fischer, C., and Meese, C.O. (1987) Eur J. Biochem. 169, 113-123) and that this might confound its use as an index of free radical generation, we sought to characterize the mechanism of its formation by human platelets. Activation of platelets by threshold concentrations of collagen, thrombin, and arachidonic acid resulted in formation of 8-epi PGF2 Alpha coincident with that of the COX product, thromboxane, and the 12 lipoxygenase product, 12-hydroxyeicosatetraenoic acid, as detected by selected ion monitoring assays using gas chromatography-mass spectrometry. The effect appeared selective for 8-epi PGF2 Alpha among the F2 isoprostanes. Pretreatment of platelets with aspirin or indomethacin abolished 8-epi PGF2 Alpha formation. COX-independent activation of platelets by high doses of collagen or thrombin, by the phorbol ester, phorbol 12-myristate 13-acetate, or the Prostaglandin endoperoxide analog, U 46619 was not associated with 8-epi PGF2 Alpha formation. Confirmation of the nature of the material formed by platelet COX as 8-epi PGF2 Alpha included its cochromatography over three highly resolving high performance liquid chromatography systems, identification by electron impact mass spectrometry, and its formation by partially purified COX. Inhibition of platelet thromboxane formation was associated with augmented 8-epi PGF2 Alpha formation. A major component of 8-epi PGF2 Alpha formed in serum by healthy volunteers was shown to be sensitive to inhibition by aspirin ex vivo. In addition to its generation by free radical catalyzed mechanisms, 8-epi PGF2 Alpha may be formed as a PG by human platelets. Given that activation of platelet COX characterizes many of the human syndromes which are putatively associated with free radical generation, assessment of the contribution of this pathway is relevant to the use of 8-epi PGF2 Alpha as an index of lipid peroxidation in vivo.
