A Premature Increase in Circulating Cortisol Suppresses Expression of 11β Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid in the Adrenal of the Fetal Sheep1

Ross, J. T.; McMillen, I. Caroline; Adams, Michael Brenton; Coulter, Catherine

doi:10.1095/biolreprod62.5.1297

Cited by 9 publications

(11 citation statements)

References 21 publications

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“…Cortisol, therefore, appears to suppress 11 -HSD2 activity in the ovine placenta during late gestation. A similar inhibitory effect of fetal cortisol on 11 -HSD2 gene expression has been observed in adrenal glands of fetal sheep close to term (Ross et al 2000). The inverse correlation observed in the present study between plasma fetal cortisol and placental 11 -HSD2 activity also indicates that fetal cortisol is a physiological regulator of the placental conversion of cortisol to cortisone and suggests that it may increase placental exposure to bioactive glucocorticoids during late gestation.…”

Section: Discussionsupporting

confidence: 87%

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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Section: Discussionsupporting

confidence: 87%

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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“…While adrenal Hsd11b2 expression has been noted previously in the rat (Smith et al 1997) and other species (Yang & Matthews 1995, Ross et al 2000, its physiological significance remains uncertain. The HSD11B2 enzyme catalyzes the conversion of corticosterone to its biologically inert, 11-keto derivative 11-dehydrocorticosterone (11-DHC), and Yang & Matthews (1995) suggested that adrenal HSD11B2 may serve to limit exposure of adrenocortical cells to very high levels of corticosterone and/or provide a source of 11-DHC for reactivation within target tissues by HSD11B1.…”

Section: Discussionmentioning

confidence: 89%

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

Waddell¹,

Bollen²,

Wyrwoll³

et al. 2010

Journal of Endocrinology

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Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0 . 75 mg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/ reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.

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“…Vascular catheters were implanted in the jugular vein of the ewe, a carotid artery, and jugular vein of the fetus, and in the amniotic cavity as previously described (Ross et al. ; Muhlhausler et al. ).…”

Section: Methodsmentioning

confidence: 99%

The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development

et al. 2013

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The prepartum surge in plasma cortisol concentrations in humans and sheep promotes fetal lung and surfactant system maturation in the support of air breathing after birth. This physiological process has been used to enhance lung maturation in the preterm fetus using maternal administration of betamethasone in the clinical setting in fetuses as young as 24 weeks gestation (term = 40 weeks). Here, we have investigated the impact of fetal intravenous cortisol infusion during the canalicular phase of lung development (from 109- to 116-days gestation, term = 150 ± 3 days) on the expression of genes regulating glucocorticoid (GC) activity, lung liquid reabsorption, and surfactant maturation in the very preterm sheep fetus and compared this to their expression near term. Cortisol infusion had no impact on mRNA expression of the corticosteroid receptors (GC receptor and mineralocorticoid receptor) or HSD11B-2, however, there was increased expression of HSD11B-1 in the fetal lung. Despite this, cortisol infusion had no effect on the expression of genes involved in lung sodium (epithelial sodium channel -α, -β, or -γ subunits and sodium–potassium ATPase-β1 subunit) or water (aquaporin 1, 3, and 5) reabsorption when compared to the level of expression during exposure to the normal prepartum cortisol surge. Furthermore, in comparison to late gestation, cortisol infusion does not increase mRNA expression of surfactant proteins (SFTP-A, -B, and -C) or the number of SFTP-B-positive cells present in the alveolar epithelium, the cells that produce pulmonary surfactant. These data suggest that there may be an age before which the lung is unable to respond biochemically to an increase in fetal plasma cortisol concentrations.

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A Premature Increase in Circulating Cortisol Suppresses Expression of 11β Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid in the Adrenal of the Fetal Sheep1

Cited by 9 publications

References 21 publications

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

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

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development

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