Pulmonary phospholipied biosynthesis and the ability of the fetal rabbit lung to reduce cortisone to cortisol during the final ten days of gestation

Nicholas, Terence E.; Johnson, Rodger G.; Lugg, Moira A.; Kim, Patricia A.

doi:10.1016/0024-3205(78)90007-3

Cited by 18 publications

(9 citation statements)

References 19 publications

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“…The timing of this "switch" is advanced by glucocorticoid administration in rodents (717) and in humans, by a pituitary factor (502), probably ACTH, driving fetal glucocorticoid secretion. Increased oxoreductase (11␤-HSD1) activity at term parallels increased phospholipid biosynthesis (518) consistent with glucocorticoid stimulation of surfactant production (43). Deficiency or inhibition of 11␤-HSD1 reduces fetal lung phospholipid and surfactant synthesis (309,310,649) and increases lung weight (649), the latter consistent with a permanent reduction in lung-to-body weight ratio following prenatal glucocorticoid exposure (667).…”

Section: Lungmentioning

confidence: 85%

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

Chapman

Holmes

Seckl

2013

Physiological Reviews

709

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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Section: Lungmentioning

confidence: 85%

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

Chapman

Holmes

Seckl

2013

Physiological Reviews

709

601

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“…During this same period the activity of 11/3-hydroxysteroid de hydrogenase in fetal lung is increasing (19,24) and the ready availability of substrate, E, in dicates that the lung and possibly other fetal organs have the means of influencing their own corticosteroid milieu.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Mulay et al (13) sampled blood from either an ear vein or via heart puncture after anesthetizing and lapa- rotomizing the rabbit. In addition, they did not mention whether blood was sampled from the right or left side of the heart: this could make an appreciable difference in view of the ability of the adult lung to reduce E to F (18,19).…”

Section: Discussionmentioning

confidence: 99%

“…The 11-keto compounds, cortisone (E) and 11-de hydrocorticosterone (A), which are inactive 1 This research was supported by a grant from the National Health and Medical Research Council of Australia. steroids in the adult, have been largely ignored. However, recent findings that the fetal lung has the ability to reduce the 11-keto to the 11-hydroxylated steroids (19,24) suggest that the concentrations of E and A could be impor tant determinants of the level of 11-hydrox ylated corticoids in tissue. In the present ex periments we have measured the concentrations of E and F in maternal and fetal blood and in amniotic fluid of rabbits during the final third of gestation.…”

Section: Introductionmentioning

confidence: 99%

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Cortisone and Cortisol in Maternal and Fetal Blood and in Amniotic Fluid during the Final Ten Days of Gestation in the Rabbit

Barr¹,

Lugg

Nicholas³

1980

Neonatology

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We have used instant thin-layer chromatography and radioimmunoassay to measure the concentrations of total cortisone (E) and cortisol (F) in the fetal and maternal compartments of the rabbit. The concentration of F in fetal blood increased markedly at day 25; this is just prior to the rapid increase in the surfactant phospholipids in lung tissue in this species. This increase coincided with a peak in the concentration of E and F in the maternal blood and may reflect the maternal levels. There was no ‘surge’ in the concentration of total F in fetal blood at term. The concentration of E in fetal blood varied between 5 and 15 ng/ml during this last stage of gestation, hence providing ready substrate for the 11β-reductase present in lung and other tissues. The concentration of E and F in maternal blood was significantly higher and more variable than that in blood from nonpregnant female rabbits, and there was a pronounced peak in concentration at day 30 (term: 31 days). The concentrations of both E and F in amniotic fluid were lower than those in either maternal or fetal blood until day 30 when the concentration of F increased fivefold to 19.2 ± 2.58 (mean ± SEM of 6 samples).

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“…At day 25 of gestation the rabbit fetal lung favours the reduction of E, with mini mal oxidation of F [15,20]. We have also found that whereas the fetal liver favoured reduction, the kidneys tended to oxidise E [unpublished observations]; the rabbit is sim ilar to the human fetus in this respect [12], Hence the final balance between 3H-E and 3H-F in the fetal blood would reflect the 11 (3-oxidase/reductase activities of the different tissues and their relative blood flows.…”

Section: Discussionmentioning

confidence: 99%

Transfer of <sup>3</sup>H-Cortisone and <sup>3</sup>H-Cortisol between the Amniotic, Allantoic, and Fetal Blood Compartments in the Rabbit at Day 25 of Gestation

Lugg¹,

Nicholas²

1983

Neonatology

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We have examined the rate of disappearance and the form of the radiolabel following the injection of either [1,2–³H]-cortisone (³H-E) or [1,2,6,7, n-³H]-cortisol (³H-F) into the amniotic sac of rabbits at day 25 of gestation. The half-life of ³H-E was approximately 35 min and was very much shorter than that of ³H-F. Concurrent with the disappearance of ³H-E was an increase in the amount of tritium in both the allantoic and the fetal blood compartments. Whereas following injection of ³H-E there was a rapid conversion of E to F that was reflected in all three compartments, following injection of ³H-F the vast majority of the tritium label remained as F. We conclude that amniotic E may act as a ready source of fetal F.

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Pulmonary phospholipied biosynthesis and the ability of the fetal rabbit lung to reduce cortisone to cortisol during the final ten days of gestation

Cited by 18 publications

References 19 publications

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

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

Cortisone and Cortisol in Maternal and Fetal Blood and in Amniotic Fluid during the Final Ten Days of Gestation in the Rabbit

Transfer of <sup>3</sup>H-Cortisone and <sup>3</sup>H-Cortisol between the Amniotic, Allantoic, and Fetal Blood Compartments in the Rabbit at Day 25 of Gestation

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