Steps of glucocorticoid action in normal and diabetic rat placenta

Heller, Claudia L.; Weisenberg, Liliana S.; Ortí, Eduardo; Nicola, Alejandro F. De

doi:10.1016/0022-4731(88)90214-2

Cited by 9 publications

(2 citation statements)

References 24 publications

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“…It was subsequently shown that up to 85% of cortisol injected into the maternal circulation eventually reached the umbilical circulation as cortisone [45]. These early data showing substantial 11␤-HSD bioactivity in the placenta have since been confirmed by extensive research in the human [35,[46][47][48][49][50][51] and in several other species including the baboon [47,[52][53][54][55], sheep [56,57], rat [9,48,[58][59][60], and pig [61].…”

Section: Placental 11␤-hsd Bioactivitymentioning

confidence: 91%

Dual Function of 11β-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action1

Burton¹,

Waddell²

1999

Biology of Reproduction

142

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Target cell metabolism of glucocorticoids is now recognized as an important modulator of ligand access to the glucocorticoid receptor (GR). This metabolism occurs via two distinct 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes (types 1 and 2) that catalyze interconversion of active glucocorticoids (cortisol and corticosterone) and their inactive 11-keto products (cortisone and 11-dehydrocorticosterone, respectively). The focus of this review is on the biology of the 11beta-HSD enzymes in the placenta, where they also regulate passage of maternal glucocorticoids to the fetus. The presence of this metabolic barrier at the maternal-fetal interface is potentially crucial to fetal growth and development, since maternal glucocorticoid levels are elevated in pregnancy and since excess glucocorticoid exposure in fetal life has detrimental effects on prenatal growth and increases susceptibility to disease in subsequent adult life. In primates, transplacental glucocorticoid passage also appears to play an important role in the induction of an autonomous fetal hypothalamic-pituitary-adrenal axis near term. Placental 11beta-HSD is also likely to modulate glucocorticoid actions within the placenta, per se, by regulating their access to placental GR. Moreover, because some progesterone effects are exerted via the GR, placental 11beta-HSD may regulate progesterone-glucocorticoid competition for access to this receptor and thereby affect the biological actions of both steroids in the placenta.

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Section: Placental 11␤-hsd Bioactivitymentioning

confidence: 91%

Dual Function of 11β-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action1

Burton¹,

Waddell²

1999

Biology of Reproduction

142

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“…p113-HSD is present in the placenta of several species [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and its activity appears to change with advancing pregnancy in both the rat [14] and baboon [8,10,11]. The primary physiological role of placental 11-HSD is generally thought to be regulation of glucocorticoid transfer between maternal and fetal compartments, and variations in its activity have been related to fetal adrenal development [10,11,17], fetal growth [12], and subsequent development of disease in adult life [3,21].…”

Section: Introductionmentioning

confidence: 99%

Zonal Distribution of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 Messenger Ribonucleic Acid Expression in the Rat Placenta and Decidua during Late Pregnancy1

Burton

Smith²,

Krozowski³

et al. 1996

Biology of Reproduction

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Glucocorticoid action in several target tissues is dependent on expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), and in the placenta 11 beta-HSD is thought to regulate transfer of active glucocorticoid to the fetus. This study compared expression of the two recognized 11 beta-HSD enzymes, types 1 and 2, in the rat placenta and decidua on Days 16 and 22 of gestation (term = Day 23). According to S1 nuclease protection analysis, although mRNA for 11 beta-HSD-1 was only just detectable in the labyrinth zone on Day 16, by Day 22 this expression had increased almost 20-fold. There was also an increase (approximately 2-fold) in 11 beta-HSD-1 mRNA in the basal zone between Days 16 and 22. In Day 16 decidua, 11 beta-HSD-1 mRNA was also highly expressed, but insufficient tissue was available for analysis on Day 22. Western blot analysis showed that immunoreactive 11 beta-HSD-1 (molecular mass 34 kDa) was present in those tissues with the highest 11 beta-HSD-1 mRNA expression (Day 16 decidua and Day 22 labyrinth zone). With respect to mRNA for 11 beta-HSD-2, high expression was observed in the decidua and labyrinth zone at Day 16, but in the latter this expression then declined 90% by Day 22. In contrast, expression of mRNA for 11 beta-HSD-2 increased more than 3-fold in the basal zone over the same period. Consistent with coexpression of the two 11 beta-HSD enzymes, both 11-oxoreductase and 11 beta-dehydrogenase bioactivity were clearly evident in all tissues, and each varied with stage of gestation. Specifically, 11 beta-dehydrogenase activity in the basal zone increased from 38 +/- 2% (mean +/- SEM) on Day 16 to 56 +/- 2% on Day 22, while 11-oxoreductase activity fell from 55 +/- 3% to 43 +/- 2% over the same period. In contrast, 11 beta-dehydrogenase activity in the labyrinth zone fell with advancing pregnancy (Day 16: 63 +/- 2%; Day 22: 48 +/- 2%). Both 11-oxoreductase (58 +/- 3%) and 11 beta-dehydrogenase (38 +/- 4%) activities were also evident in decidua at Day 16. In conclusion, this study shows that expression of 11 beta-HSD-1 and -2 is zone-specific in the placenta and maternal decidua. Moreover, opposite changes in the expression of the two enzymes occur in the basal and labyrinth zones of the placenta over the last days of pregnancy, indicative of distinct regulatory mechanisms and functional significance for the enzymes in the two placental zones.

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Placental metabolism and its regulation in health and diabetes

Desoyé

Shafrir

1994

Molecular Aspects of Medicine

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Steps of glucocorticoid action in normal and diabetic rat placenta

Cited by 9 publications

References 24 publications

Dual Function of 11β-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action1

Dual Function of 11β-Hydroxysteroid Dehydrogenase in Placenta: Modulating Placental Glucocorticoid Passage and Local Steroid Action1

Zonal Distribution of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 Messenger Ribonucleic Acid Expression in the Rat Placenta and Decidua during Late Pregnancy1

Placental metabolism and its regulation in health and diabetes

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