Local Modulation by 11 -Hydroxysteroid Dehydrogenase of Glucocorticoid Effects on the Activity of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion and Placental Trophoblast Cells

Patel, Falguni A.

doi:10.1210/jc.84.2.395

Cited by 25 publications

(26 citation statements)

References 39 publications

(71 reference statements)

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“…PGDH mRNA expression is increased by progesterone (23). The inhibitory effect of cortisol on PGDH activity seems to be mediated by the mineralocorticoid receptor, as has been demonstrated recently (15,24). We found a positive correlation between 11b-HSD2 and PGDH mRNA expression.…”

Section: Discussionsupporting

confidence: 81%

“…Glucocorticoids inhibit PGDH enzyme activity in cultured human placental syncytiotrophoblast and chorion trophoblast cells (15). PGDH mRNA expression is increased by progesterone (23).…”

Section: Discussionmentioning

confidence: 99%

“…In a dose-dependent manner, cortisol decreases 15-hydroxyprostaglandin dehydrogenase (PGDH) activity and mRNA expression in placental and chorion trophoblast cells (15). The enzyme inactivates prostaglandin E 2 (PGE 2 ) and PGF 2a by formation of 15-ketoprostaglandins in placenta and chorion.…”

Section: Introductionmentioning

confidence: 99%

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Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

Schoof¹,

Girstl²,

Frobenius

et al. 2001

European Journal of Endocrinology

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Background: During human pregnancy, 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11b-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. Objective: To examine developmental changes in placental 11b -HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. Methods: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11b-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. Results: Placental mRNA expression of 11b-HSD2 and PGDH increased signi®cantly with gestational age r 0X55Y P 0X0002 and r 0X42Y P 0X007X In addition, there was a signi®cant correlation between the two enzymes r 0X58Y P , 0X0001X Conclusions: In the course of pregnancy there is an increase in 11b-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11b-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11b-HSD2 upregulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.

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Section: Discussionsupporting

confidence: 81%

“…Glucocorticoids inhibit PGDH enzyme activity in cultured human placental syncytiotrophoblast and chorion trophoblast cells (15). PGDH mRNA expression is increased by progesterone (23).…”

Section: Discussionmentioning

confidence: 99%

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Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

Schoof¹,

Girstl²,

Frobenius

et al. 2001

European Journal of Endocrinology

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“…Since there is no change in either the dehydrogenase or reductase activity of placental 11 -HSD1 during late gestation , the fall in placental 11 -HSD2 activity observed during the last 15-20 days of gestation in the present study represents a 15-20% decrease in total dehydrogenase activity of the placenta. This fall in placental cortisol to cortisone conversion will enhance the placental effects of rising fetal cortisol concentrations close to term and lead to increased activation of the glucocorticoid-dependent enzymes involved in placental oestrogen synthesis (Sun et al 1998a, Burton & Waddell 1999, Patel et al 1999. The prepartum fall in placental 11 -HSD2 activity may, therefore, form part of the endocrine cascade responsible for initiating ovine parturition and contribute to the positive feedback mechanisms that operate during late gestation to ensure delivery of viable lambs at term.…”

Section: Discussionmentioning

confidence: 99%

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

Clarke

Ward²,

Forhead³

et al. 2002

Journal of Endocrinology

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The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 -hydroxysteroid dehydrogenase (11 -HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 -HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 -HSD2 activity decreased between 128-132 days and term (]145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128-132 days of gestation reduced placental 11 -HSD2 activity to term values. In contrast, 11 -HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 -HSD2 activity, expressed both on a weight-specific basis and per mg placental protein.Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 -HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

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“…Here, glucocorticoids increase prostaglandin E 2 production, which is central to the induction of parturition. 11␤-HSD1 is also expressed in human chorion cells where glucocorticoids inhibit prostaglandin catabolism by repressing the gene encoding 15-hydroxy-PG dehydrogenase (546). Thus 11␤-HSD1 amplification of glucocorticoid action reduces prostaglandin breakdown, further increasing the parturition signal.…”

Section: Localization and Ontogeny Of Placental 11␤-hsd2mentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

735

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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Local Modulation by 11 -Hydroxysteroid Dehydrogenase of Glucocorticoid Effects on the Activity of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion and Placental Trophoblast Cells

Cited by 25 publications

References 39 publications

Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

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