Paradoxical stimulation of both lipocortin and prostaglandin production in human amnion cells by dexamethasone

Mitchell, Murray D.; Lytton, Fiona D. C.; Varticovski, Lyuba

doi:10.1016/0006-291x(88)90569-4

Cited by 59 publications

(19 citation statements)

References 12 publications

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“…The situation in vivo or in cells ex vivo also seems complex: Northup et al, (1988) were unable to detect an increase in lipocortin 1 protein in mouse macrophages following glucocorticoid treatment but Mitchell et al (1988) detected an increase in lipocortin 1 in human amnion cells following dexamethasone treatment. In man, Goulding et al (1990) reported an increase in monocyte lipocortin 1 following intravenous injection of hydrocortisone and Browning et al (1990) described de novo synthesis of lipocortin 1 in primary cultures of peripheral monocytes maintained in the presence of glucocorticoids.…”

Section: Induction Of Lipocortins In Rat Leucocytes 67mentioning

confidence: 99%

Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

Peers

Smillie

Elderfield

et al. 1993

British J Pharmacology

107

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1 We have studied the occurrence, distribution and disposition of lipocortins (annexins) 1, 2 and 5 in mixed peritoneal leucocytes obtained from rats in which glucocorticoid levels were altered by adrenalectomy, administration of the glucocorticoid antagonist, RU486, or by injection of dexamethasone or hydrocortisone, as well as from rats in which the peritoneal cells were elicited by inflammatory stimuli. 2 In cells obtained from untreated rats with an intact adrenal cortex, lipocortins 1, 2 and 5 were readily detectable: the majority of each of the proteins was apparently located intracellularly with much smaller amounts in the membrane. Lipocortin 1 and to a lesser extent lipocortin 5 were also seen in a Ca2'-dependent association with the external plasma membrane. Following administration of RU486(2 x 20 mg kg-1) the amounts of lipocortin 1 and 2 in cells were greatly reduced. Conversely, injection of hydrocortisone (1 mg kg-') or dexamethasone (0.08 mg kg-1) caused an increase in the amount of lipocortin 1 and 2 in peritoneal cells within 30 min. Lipocortin 5 was unchanged by any manipulation of glucocorticoid levels. 3 Lipocortins 1 and 2 were elevated in both intracellular and membrane-associated fractions of macrophages elicited by intraperitoneal injection in inflammogens. This phenomenon also occurred in adrenalectomized animals. 4 Our data indicate that glucocorticoids control the synthesis of some members of the lipocortin family in rat mixed peritoneal cells but also suggest the existence of a separate system for controlling the generation of this protein. The significance of these observations is considered in relation to the mechanism of glucocorticoid hormone action on eicosanoid production.

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Section: Induction Of Lipocortins In Rat Leucocytes 67mentioning

confidence: 99%

Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

Peers

Smillie

Elderfield

et al. 1993

British J Pharmacology

107

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“…Dexamethasone, a glucocorticoid receptor agonist, has been shown to stimulate PGE 2 formation by human amnion cells in culture (Mitchell et al 1988, Potestio et al 1988. Similarly, PGF 2 production increases several-fold in maternal placental cotyledons and uterine venous plasma following labour induction in the ewe (Liggins & Grieves 1971).…”

Section: Introductionmentioning

confidence: 99%

Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour

McLaren

Young²,

Rice

2000

Journal of Endocrinology

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Parturition in the ewe is preceded by an increase in the synthesis of prostaglandins (PGs) by gestational tissues. To establish the uterine source of these PGs, placental cotyledons, fetal membranes and maternal uterine tissues were collected from ewes (n=6) at spontaneous parturition. Solubilised tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PG G/H synthase-1 and -2 (PGHS-1 and PGHS-2). PGHS-1 was expressed by all intrauterine tissues at term labour. Densitometric analysis of Western blot autoradiographs showed that the fetal membranes and maternal cervix contained the largest amounts of PGHS-1. PGHS-1 enzyme content of ovine amnion was significantly greater than that of either chorion or allantois (P<0·05). PGHS-1 protein content of myometrial, endometrial and cotyledonary tissue extracts was minimal. Formation of the PGHS-2 isozyme was confined to placental tissue at term labour. PGHS-2 protein levels in sheep placenta were significantly higher than those of PGHS-1 in all intrauterine tissues examined. This result supports the hypothesis that PGHS-2 is a major contributor to PG formation at term labour.To elucidate the developmental changes in PGHS-1 and PGHS-2 relative to labour onset, an experimental paradigm of glucocorticoid-induced delivery was used. Previous characterisation and validation of this labour model demonstrated that direct, transabdominal, intrafetal injection of the synthetic glucocorticoid betamethasone (5·7 mg in 1 ml aqueous vehicle) on day 131 of gestation induced labour onset in 56·6 0·8 h (mean ...). As the latent period to induced-labour was known, the time course of enzyme formation could be ascertained. Sheep (n=20) were killed by barbiturate injection at various time intervals post-injection (0, 14, 28, 42 and 56 h). Tissue extracts collected at post-mortem examination were prepared and analysed by Western blots. PGHS-2 was induced in ovine cotyledon in a time-dependent fashion following glucocorticoid injection (P<0·05). There was a 12-fold increase in abundance between the time of betamethasone administration (0 h) and established labour (56 h). The PGHS-2 isozyme was not detected in any of the other tissues examined. In contrast, formation of the PGHS-1 isozyme did not change in relation to inducedlabour in any of the intrauterine tissues. This finding is consistent with constitutive formation of PGHS-1.Previous studies have demonstrated a rise in PG production in association with glucocorticoid-induced labour and spontaneous delivery. The results of the present study indicate that this rise in PG production is due to increased formation of the PGHS-2 isozyme in ovine cotyledon. PGHS-2 appears to be induced by exogenous glucocorticoid administration and/or the mechanisms controlling ovine parturition. The role of PG formation by the fetal membranes is yet to be elucidated.

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“…In one study, Mitchell et al (1988) demonstrated enhanced lipocortin and prostaglandin synthesis in cultured cells from human amnion. However, Gibb & Lavoie (1990) in a later study found that the inhibitory effect of dexamethasone on prostaglandin synthesis by human amnion cells depended on whether or not the cells were freshly cultured or had been cultured for several days.…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoids are well characterized anti-inflammatory agents that are reported to inhibit PLA2 through induction and release of lipocortins (Hirata et al, 1980;Blackwell et al, 1982). However, the antiphospholipase activity of lipocortins is controversial as in some systems, synthesis of lipocortins is coincidental with no change or an increase in phospholipid hydrolysis (Duval et al, 1986;Northup et al, 1988;Mitchell et al, 1988). We isolated and characterized a PLA2 inhibitor, gravidin (Wilson & Christie, 1991) that has been linked with maintenance of human pregnancy (Wilson et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Decreased inhibition by gravidin of arachidonate release from transformed compared to nontransformed cells

Wilson

Ralph

Ganendren

1992

British J Pharmacology

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Paradoxical stimulation of both lipocortin and prostaglandin production in human amnion cells by dexamethasone

Cited by 59 publications

References 12 publications

Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucocorticoid-induced and spontaneous labour

Decreased inhibition by gravidin of arachidonate release from transformed compared to nontransformed cells

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