Leukocytes modulate 11β-hydroxysteroid dehydrogenase (11β-HSD) activity in human granulosa-lutein cell cultures

Evagelatou, Marianthi; Peterson, Sharon; Cooke, Brian A.

doi:10.1016/s0303-7207(97)00146-9

Cited by 24 publications

(7 citation statements)

References 31 publications

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“…Furthermore, in the rat ovary, gonadotrophins can have both a stimulatory effect on 11β‐HSD1 expression and an inhibitory effect on 11β‐HSD2 expression, (26) though the cellular localization of the isozymes was not determined. In a study of human granulosa‐lutein cell cultures, 11β‐HSD1 activity appeared to be dependent on the presence of leukocytes within these cultures (27) . When leukocytes were removed from the culture, activity fell, suggesting a stimulatory, probably cytokine‐mediated, effect.…”

Section: Discussionmentioning

confidence: 99%

Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Proinflammatory Cytokines in Osteoblasts: An Autocrine Switch from Glucocorticoid Inactivation to Activation

Cooper

Bujalska

Rabbitt

et al. 2001

Journal of Bone and Mineral Research

210

129

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Tissue damage by proinflammatory cytokines is attenuated at both systemic and cellular levels by counter anti-inflammatory factors such as corticosteroids. Target cell responses to corticosteroids are dependent on several factors including prereceptor regulation via local steroidogenic enzymes. In particular, two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), by interconverting hormonally active cortisol (F) to inactive cortisone (E), regulate the peripheral action of corticosteroids 11beta-HSD1 by converting E to F and 11beta-HSD2 by inactivating F to E. In different in vitro and in vivo systems both 11beta-HSD isozymes have been shown to be expressed in osteoblasts (OBs). Using the MG-63 human osteosarcoma cell-line and primary cultures of human OBs, we have studied the regulation of osteoblastic 11beta-HSD isozyme expression and activity by cytokines and hormones with established roles in bone physiology. In MG-63 cells, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) potently inhibited 11beta-HSD2 activity (cortisol-cortisone conversion) and messenger RNA (mRNA) levels in a dose-dependent manner while stimulating reciprocal expression of 11beta-HSD1 mRNA and activity (cortisone-cortisol conversion). A similar rise in 11beta-HSD1 reductase activity also was observed in primary cultures of OBs treated with 10 ng/ml TNF-alpha. Pretreatment of MG-63 cells with 0.1 ng/ml IL-1beta resulted in increased cellular sensitivity to physiological glucocorticoids as shown by induction of serum and glucocorticoid-inducible kinase (SGK; relative increase with 50 nM F but no IL-1beta pretreatment 1.12 +/- 0.34; with pretreatment 2.63 +/- 0.50; p < 0.01). These results highlight a novel mechanism within bone cells whereby inflammatory cytokines cause an autocrine switch in intracellular corticosteroid metabolism by disabling glucocorticoid inactivation (11beta-HSD2) while inducing glucocorticoid activation (11beta-HSD1). Therefore, it can be postulated that some of the effects of proinflammatory cytokines within bone (e.g., periarticular erosions in inflammatory arthritis) are mediated by this mechanism.

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Section: Discussionmentioning

confidence: 99%

Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Proinflammatory Cytokines in Osteoblasts: An Autocrine Switch from Glucocorticoid Inactivation to Activation

Cooper

Bujalska

Rabbitt

et al. 2001

Journal of Bone and Mineral Research

210

129

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“…It has been reported that the estrous cycles in interleukin (IL)-2 gamma-chain KO mice were irregular compared with wild-type mice . Macrophage/leukocyte-derived IL-5 significantly increased the 11 beta-hydroxysteroid dehydrogenase activity in granulosa cells (Evagelatou et al 1997). Thus, leukocytes interact with the ovarian cells through cytokine secretion and/or cell-cell contact to regulate steroidogenesis in human granulosa cells.…”

Section: Cytokinesmentioning

confidence: 94%

Reproductive failure in mice lacking inter-alpha-trypsin inhibitor (ITI) – ITI target genes in mouse ovary identified by microarray analysis

Suzuki¹,

Kobayashi²,

Tanaka³

et al. 2004

Journal of Endocrinology

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Bikunin, a Kunitz-type protease inhibitor, is found in blood and urine. It has been established by two laboratories independently that the bikunin knockout female mice display a severe reduction in fertility: the cumulus oophorus has a defect in forming the extracellular hyaluronanrich matrix during expansion. Proteins of the inter-alphatrypsin inhibitor (ITI) family are eliminated in mice in which the bikunin gene has been inactivated, since bikunin is essential for their biosynthesis. Proteins of the ITI family may contribute to the microenvironment in which ovulation takes place. It is not clear, however, whether a single mechanism affects the reproductive function including ovulation. For identifying the full repertoire of the ITI deficiency-related genes, a cDNA microarray hybridization screening was conducted using mRNA from ovaries of wild-type or bik / female mice. A number of genes were identified and their regulation was confirmed by real-time RT-PCR analysis. Our screen identified that 29 (0·7%) and 5 genes (0·1%) of the genes assayed were, respectively, up-and down-regulated twofold or more. The identified genes can be classified into distinct subsets. These include stress-related, apoptosis-related, proteases, signaling molecules, agingrelated, cytokines, hyaluronan metabolism and signaling, reactive oxygen species-related, and retinoid metabolism, which have previously been implicated in enhancing follicle development and/or ovulation. Real-time RT-PCR analysis confirmed that these genes were up-and down-regulated two-to tenfold by bikunin knockout. These studies demonstrate that proteins of the ITI family may exert potent regulatory effects on a major physiological reproductive process, ovulation.

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“…Based on the evidence that we have collected, we speculate that a maternal systemic inflammatory factor induced by asthma, which can be inhibited by inhaled glucocorticoid use, may alter placental 11β-HSD 2 activity. Previous work on human 11β-HSD in vitro indicates that cytokines and prostaglandins downregulate 11β-HSD gene expression (Alfaidy et al 2001;Cooper et al 2001;Evagelatou et al 1997) thereby increasing intracellular cortisol concentrations and modulating the inflammatory response. One question arising from these data is whether the changes observed in placental 11β-HSD 2 activity in female placentae result in an alteration of intracellular cortisol concentrations.…”

Section: Glucocorticoid Effects On Fetal Growthmentioning

confidence: 99%

Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth

Clifton

2005

Cell Tissue Res

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Human pregnancy is associated with sexually dimorphic differences in mortality and morbidity of the fetus with the male fetus experiencing the poorest outcome following complications such as pre-eclampsia, pre-term delivery and infection. The physiological mechanisms that confer these differences have not been well characterised in the human. Work conducted on the effect of maternal asthma during pregnancy, combining data collected from the mother, placenta and fetus has found some significant sex-related mechanistic differences associated with fetal growth in both normal pregnancies and pregnancies complicated by asthma. Specifically, sexually dimorphic differences have been found in placental glucocorticoid metabolism in male and female fetuses of normal pregnancies. In response to the presence of maternal asthma, only the female fetus alters placental glucocorticoid metabolism resulting in decreased growth. The male fetus does not alter placental function or growth in response to maternal asthma. As a result of the alterations in glucocorticoid metabolism in the female, downstream changes occur in pathways regulated by glucocorticoids. These data suggest that the female fetus adjusts placental function and reduces growth to compensate for maternal disease. However, the male fetus continues to grow in response to maternal asthma with no changes in placental function. This response by the male fetus may partially contribute to the increased risk of morbidity and mortality in this sex.

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Leukocytes modulate 11β-hydroxysteroid dehydrogenase (11β-HSD) activity in human granulosa-lutein cell cultures

Cited by 24 publications

References 31 publications

Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Proinflammatory Cytokines in Osteoblasts: An Autocrine Switch from Glucocorticoid Inactivation to Activation

Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Proinflammatory Cytokines in Osteoblasts: An Autocrine Switch from Glucocorticoid Inactivation to Activation

Reproductive failure in mice lacking inter-alpha-trypsin inhibitor (ITI) – ITI target genes in mouse ovary identified by microarray analysis

Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth

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