Effects of sustained hypoxaemia with 72 hours recovery on 11β-hydroxysteroid dehydrogenase types 1 and 2 gene expression in near-term fetal sheep

1997 ◽  
Vol 9 (8) ◽  
pp. 755 ◽  
Author(s):  
H. Asano ◽  
K. Shearman ◽  
A. Darnel ◽  
B. S. Richardson ◽  
K. Yang
Keyword(s):  
Metabolic Acidosis ◽  
Fetal Liver ◽  
Time Lag ◽  
Placental Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Tissue Level ◽  
Fetal Sheep ◽  
Liver And Kidney ◽  
Near Term ◽  
Inspired Oxygen

The study examined the effects of 8 h sustained hypoxaemia, with 72 h recovery, on the expression of 11β-hydroxysteroid dehydrogenase (11b-HSD) types 1 and 2 in near-term fetal sheep. Placental tissue and fetal liver and kidney were collected at Days 135–138 gestation 72 h after 8 h sustained hypoxaemia induced by lowering maternal inspired oxygen with (n= 9) and without (n = 6) metabolic acidosis or after 8 h normoxia (n = 6). In hypoxic fetuses with metabolic acidosis, a significant increase in the level of 11β-HSD2 mRNA in the kidney compared with controls was correlated significantly with degree of associated fetal acidaemia, but there were no corresponding increases in the tissue level of 11β-HSD2 activity. Hence, a time lag may exist between the mRNA and activity. Alternatively, the translation of 11β-HSD2 mRNA may be inhibited. In contrast, levels of 11β-HSD1 mRNA in the placenta and fetal liver were unchanged 72 h after sustained hypoxaemia. These results indicate that sustained fetal hypoxaemia with metabolic acidosis selectively up-regulates 11β-HSD2 mRNA expression in the near-term fetal sheep kidney. This may be a re-bound effect at 72 h following an initial down-regulation as observed in a previous study.

Differential expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in the developing ovine fetal liver and kidney

1995 ◽  
Vol 147 (3) ◽  
pp. 405-411 ◽  
Author(s):  
D A Langlois ◽  
S G Matthews ◽  
M Yu ◽  
K Yang
Keyword(s):  
Dehydrogenase Activity ◽  
Fetal Liver ◽  
Reductase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Fetal Kidney ◽  
Fetal Sheep ◽  
Parallel Increase ◽  
Tissue Homogenates ◽  
Liver And Kidney ◽  
Ovine Fetal

Abstract In adult mammals, liver and kidney are the two major sites of biosynthesis for 11β-hydroxysteroid dehydrogenase (11β-HSD) 1 and 2 respectively. In the present study, the expression of these two isozymes in the developing ovine fetal liver and kidney was characterized. Livers and kidneys were obtained from fetal sheep at days 85, 100–120 and 140–143 of gestation (term=145 days). Tissue levels of 11β-HSD2 mRNA were assessed by Northern blot analysis. 11β-HSD dehydrogenase and reductase activities in tissue homogenates were determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates respectively. The unidirectional 11β-HSD2 dehydrogenase activity was identified by its distinct co-factor preference (NAD), and by its unique ability to metabolize dexamethasone (Dex). In the liver, 11β-HSD1 dehydrogenase and reductase activities were present by day 85, and their levels did not change between days 85 and 100–120 but increased more than twofold at days 140–143. This was consistent with changes we reported previously in the fetal hepatic 11β-HSD1 mRNA. 11β-HSD1 reductase activity was always higher than the dehydrogenase activity. 11β-HSD2 mRNA and activity were undetectable in the fetal liver at all three ages. By contrast, 11β-HSD2 mRNA was present in the fetal kidney by day 85, and its abundance increased progressively thereafter. There was a parallel increase in the renal 11β-HSD2 activity. Dex was also converted to 11-dehydro-Dex by the fetal kidney. In keeping with the absence of the full-length 11β-HSD1 mRNA, 11β-HSD1 activity was undetectable in the kidney. These results indicate that (1) 11β-HSD1 and 2 genes are differentially expressed and regulated in the fetal liver and kidney during development, (2) since the hepatic 11β-HSD1 reductase activity is always higher than the dehydrogenase activity, the fetal liver may be a potential extra-adrenal source of cortisol, and (3) 11β-HSD2 in the kidney may play a very important role in protecting the fetus from elevated levels of bioactive glucocorticoids. Journal of Endocrinology (1995) 147, 405–411

Gestational changes in fetal renal and hepatic angiotensinogen mRNA and protein

1998 ◽  
Vol 10 (5) ◽  
pp. 399 ◽  
Author(s):  
David Y. Zhang ◽  
Eugenie R. Lumbers ◽  
June J. Wu
Keyword(s):  
Fetal Liver ◽  
Rnase Protection Assay ◽  
Protein Product ◽  
Late Gestation ◽  
Protection Assay ◽  
Rnase Protection ◽  
Fetal Sheep ◽  
Protein Levels ◽  
Adult Kidney ◽  
Liver And Kidney

The aim of the study was to determine the amount of angiotensinogen expression and its protein product in fetal sheep liver and kidney in the last third of gestation. Angiotensinogen mRNA was measured by RNase protection assay and its protein levels were measured by radioimmunoassay. Levels were measured at 80, 95, 111, 125 and 139 days. Angiotensinogen mRNA was present in all fetal liver and kidney samples tested. The ratio of hepatic angiotensinogen mRNA/18 S rRNA increased by 100% (P<0.001) and angiotensinogen levels increased by 33% (P<0.001) in fetal sheep from 80 to 139 d. Over the same period the ratio of renal angiotensinogen mRNA/18 S rRNA increased by 170% (P<0.001) and renal angiotensinogen protein increased by 41% (P<0.001). The levels of angiotensinogen mRNA and its protein in the adult kidney were less than in kidneys of 139 d old fetuses (P<0.01). There was a direct relationship between levels of angiotensinogen mRNA and its protein in the liver (r = 0.53, P<0.01, n = 25) and in the kidney (r = 0.75, P<0.0001, n = 24). These findings demonstrate that there is a significant increase in both hepatic and renal angiotensinogen gene expression in the last third of gestation in the fetal sheep and that this increase is associated with an increase of angiotensinogen levels in both tissues. This increase in angiotensinogen in late gestation could influence the activity of both the intrarenal and circulating renin angiotensin systems.

scholarly journals Activities of branched-chain amino acid aminotransferase and branched-chain 2-oxo acid dehydrogenase complex in tissues of maternal and fetal sheep

1987 ◽  
Vol 242 (1) ◽  
pp. 305-308 ◽  
Author(s):  
G W Goodwin ◽  
W Gibboney ◽  
R Paxton ◽  
R A Harris ◽  
J A Lemons
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Fetal Liver ◽  
Fetal Sheep ◽  
Acid Dehydrogenase ◽  
Branched Chain Amino Acid ◽  
Maternal Liver ◽  
Liver And Kidney ◽  
Branched Chain ◽  
Fetal Muscle

Branched-chain amino acid aminotransferase (BCAAT) and branched-chain 2-oxo acid dehydrogenase (BCODH) activities were determined in sheep maternal and fetal liver, kidney, skeletal muscle, adipose and placenta in the fed and 5-day-starved states at 125 days gestation (term is 147 days). BCAAT activities were quite low in maternal skeletal muscle, low in fetal and maternal liver, high in fetal muscle, and very high in placenta. No significant changes occurred with maternal starvation. The high BCAAT activity of the placenta may provide the essential branched-chain 2-oxo acids for the fetus. BCODH activity was highest in liver and kidney of both the mother and fetus; it was largely in the active (dephosphorylated) state in maternal liver and kidney, and in fetal kidney, and about 50% active in fetal liver. The enzyme was largely inactive in fetal muscle, and about 50% active in maternal muscle. Although starvation had little effect on the activity of BCODH in fetal tissues, a significant decrease in activity was observed in maternal tissues, thereby potentially sparing branched-chain amino acids or the corresponding 2-oxo acids for maintenance of the fetus during compromised maternal nutrition.

11β-Hydroxysteroid dehydrogenase in the rat placenta: developmental changes and the effects of altered glucocorticoid exposure

1994 ◽  
Vol 143 (3) ◽  
pp. 505-513 ◽  
Author(s):  
P J Burton ◽  
B J Waddell
Keyword(s):  
Enzyme Activity ◽  
Dehydrogenase Activity ◽  
Placental Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Developmental Changes ◽  
Hypothalamic Pituitary Adrenal ◽  
Dexamethasone Acetate ◽  
Near Term ◽  
Percentage Conversion ◽  
Made In

Abstract The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) catalyses the interconversion of corticosterone, the major glucocorticoid of the rat, and the biologically-inactive 11-dehydrocorticosterone. In the placenta, 11β-HSD is thought to regulate glucocorticoid transport between maternal and fetal compartments, and may also affect the local action of glucocorticoids. The present study assessed whether 11β-dehydrogenase (corticosterone to 11-dehydrocorticosterone) and 11-oxoreductase (11-dehydrocorticosterone to corticosterone) activities are both present in rat placenta, and whether these activities change with advancing pregnancy. Enzyme activity was estimated on days 16, 19 and 22 of pregnancy (term=day 23) in placental fragments incubated for 6 h with either [3H]corticosterone or [3H] 11-dehydrocorticosterone. The percentage conversion of these substrates to [3H] 11-dehydrocorticosterone and [3H] corticosterone, respectively, were determined at the end of the incubation. Both 11-oxoreductase and 11β-dehydrogenase activities were clearly evident in placental tissue fragments, and while 11-oxoreductase activity declined with advancing pregnancy (P<0·01), 11β-dehydrogenase activity increased (P<0·01). Thus, 11-oxoreductase exceeded (P<0·05) 11β-dehydrogenase at day 16, but thereafter activities were similar. These changes do not appear to be glucocorticoid-induced, since pretreatment of rats with either metyrapone or dexamethasone acetate from day 15 of pregnancy did not affect placental 11β-HSD on day 22. To allow comparison with earlier studies, estimates of 11β-HSD were also made in placental homogenates at each stage of pregnancy. In contrast to observations in placental fragments, 11β-dehydrogenase was always the dominant reaction in homogenates, presumably due to the loss of 11-oxoreductase activity following tissue homogenisation. These data demonstrate that net 11β-dehydrogenase activity in the rat placenta increases towards term, thereby increasing the capacity for placental inactivation of active glucocorticoid. This pattern of 11β-HSD is consistent with reduced transfer of active glucocorticoid between the mother and fetus near term, and thus should promote independence of their hypothalamic-pituitary-adrenal axes. Journal of Endocrinology (1994) 143, 505–513

Localization of renin substrate in fetoplacental tissue

1990 ◽  
Vol 123 (1) ◽  
pp. 113-117 ◽  
Author(s):  
Kaj P. Metsärinne ◽  
Fredrika Pekonen ◽  
Frej Y. Fyhrquist
Keyword(s):  
Fetal Liver ◽  
Renin Angiotensin System ◽  
Placental Tissue ◽  
Renin Substrate ◽  
Angiotensin System ◽  
Human Fetal Liver ◽  
Polyclonal Rabbit ◽  
Human Renin ◽  
Liver And Kidney ◽  
Human Decidua

Abstract Specific polyclonal rabbit anti-human renin substrate-antibodies were used in order to study the distribution of renin substrate immunoreactivity in human fetal and placental tissue. Renin substrate was immunohistochemically detected in human decidua and placenta, as well as in 19 weeks old human fetal liver and kidney. The presence of renin substrate in fetoplacental tissue supports the concept of a locally functioning renin-angiotensin system.

Low-dose cortisol infusion increases plasma corticosteroid-binding globulin (CBG) and the amount of hepatic CBG mRNA in fetal sheep on day 100 of gestation

1994 ◽  
Vol 140 (3) ◽  
pp. 425-430 ◽  
Author(s):  
E T M Berdusco ◽  
W K Milne ◽  
J R G Challis
Keyword(s):  
Plasma Cortisol ◽  
Low Dose ◽  
Binding Capacity ◽  
Fetal Liver ◽  
Physiological Changes ◽  
Fetal Sheep ◽  
Corticosteroid Binding Globulin ◽  
Near Term ◽  
Synthetic Glucocorticoids ◽  
Sheep Fetus

Abstract Synthetic glucocorticoids stimulate the production of corticosteroid-binding globulin (CBG) by the liver of the sheep fetus near term (day 145). We have examined whether physiological changes in plasma cortisol alter plasma CBG concentrations, patterns of glycosylation and the amount of hepatic CBG mRNA at earlier times during pregnancy (day 100), prior to the activation of fetal hypothalamic-pituitary-adrenal function. Cortisol was infused into chronically catheterized sheep fetuses in amounts that raised the plasma cortisol concentration by about 15 nmol/l. This treatment resulted in a significant increase in the plasma corticosteroid-binding capacity and in the amount of CBG mRNA in the fetal liver, but did not alter the proportion of CBG retained using Concanavalin A chromatography. We conclude that the CBG gene in the liver of fetal sheep responds to physiological changes in plasma concentration of cortisol and we speculate that the rise in plasma CBG concentration is important in diminishing the negative feedback effect of circulating cortisol on the fetal pituitary and hypothalamus. Journal of Endocrinology (1994) 140, 425–430

Ontogeny of 11 beta-hydroxysteroid dehydrogenase in ovine fetal kidney and lung

1995 ◽  
Vol 7 (5) ◽  
pp. 1329 ◽  
Author(s):  
CE Wood ◽  
R Srun
Keyword(s):  
Gestational Age ◽  
High Sensitivity ◽  
Fetal Lung ◽  
Hydroxysteroid Dehydrogenase ◽  
Significant Activity ◽  
Fetal Kidney ◽  
Pulmonary Tissue ◽  
Fetal Sheep ◽  
Near Term ◽  
Ovine Fetal

Eleven-beta-hydroxysteroid dehydrogenase (11 beta-HSD) is an enzyme which degrades 11-hydroxycorticosteroids to biologically inactive 11-oxocorticosteroids (cortisone and 11-dehydrocorticosterone). In some tissues, the activity of this enzyme prevents binding of cortisol to mineralocorticoid receptors. The present experiments were designed to test the hypothesis that the fetal kidney contains 11 beta-HSD, that the activity of 11 beta-HSD in fetal kidney increases near term, and that the fetal lung does not contain significant 11 beta-HSD activity. In kidney and lung tissue from 23 fetal sheep ranging in age between 86 and 145 days' gestation, we measured 11 beta-HSD activity. We found significant activity in fetal kidney (14-85% conversion from cortisol to cortisone) but no measurable activity in fetal lung (0-9%). The activity of 11 beta-HSD was significantly related to fetal gestational age (r = 0.76, n = 14). We conclude that 11 beta-HSD activity in the fetal kidney develops as a function of fetal gestational age, and that activity cannot be demonstrated in fetal lung. We speculate 11 beta-HSD in the fetus might function to alter the sensitivity of target organs to glucocorticoids, as well as to mineralocorticoids, and that the absence of activity in the lung allows a high sensitivity of pulmonary tissue to cortisol at the end of gestation.

Opposite effects of glucocorticoid on hepatic 11 β-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep

1994 ◽  
Vol 143 (1) ◽  
pp. 121-126 ◽  
Author(s):  
K Yang ◽  
E T M Berdusco ◽  
J R G Challis
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Reductase Activity ◽  
Mrna Level ◽  
Hydroxysteroid Dehydrogenase ◽  
Fetal Life ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Hepatic Level

Abstract The level of 11 β-hydroxysteroid dehydrogenase (11β-HSD) mRNA in the fetal sheep liver increases dramatically between day 130 and term (term=day 145), but the causal factors remain unknown. The present study was designed to determine the effects of exogenous glucocorticoid on the fetal hepatic 11 β-HSD gene expression. Dexamethasone (dex; 2 μg/min over 15 min every 2 h) or saline was infused into chronically-catheterized fetal sheep at day 130 of gestation for 4 days. At the end of infusion, the lower right lobe of the liver was collected, total cellular RNA extracted and subjected to Northern blot analysis. It was found that the level of the hepatic 11 β-HSD mRNA in dex-treated fetuses was about four times higher than that in the saline-treated controls. To examine whether changes occur in the response of hepatic 11 β-HSD gene expression to glucocorticoids in adulthood, we also treated non-pregnant ewes with dex (10 mg/day) for 4 days. By contrast, this treatment regime in adult sheep produced a small but significant decrease in hepatic 11 β-HSD mRNA levels. We also determined whether age-specific changes in the hepatic level of 11 β-HSD mRNA following dex treatment were reflected in the level of 11 β-HSD enzyme activity. Hepatic 11 β-HSD activity was determined by a standard in vitro conversion assay using cortisol and cortisone as physiological substrates. In both fetal and adult livers, 11-oxoreductase activity (cortisone→cortisol) was predominant. Following dex treatment, there was a significant increase in the fetal hepatic level of both 11β-dehydrogenase (cortisol→cortisone) and 11-oxoreductase activities. Furthermore, the C-11 activation index, an indicator of glucocorticoid net gain, was also increased in the fetal liver by dex. In marked contrast, dex treatment in the adult did not alter the C-11 activation index though it produced a significant decrease in the hepatic level of both 11 β-dehydrogenase and reductase activities. In summary, these results indicate that (1) exogenous glucocorticoid exerts opposite effects on hepatic 11 β-HSD gene expression in fetal and adult sheep; (2) dex-induced age-specific changes in the level of 11β-HSD mRNA are carried though to the level of 11β-HSD protein; and (3) since 11 β-HSD reductase activity is predominant in both fetal and adult sheep livers, the liver may be a potential extra-adrenal source of cortisol. Furthermore, we speculate that (1) the dramatic increase in the fetal hepatic 11 β-HSD mRNA level at term may be due to the elevated fetal plasma concentration of glucocorticoid; and (2) glucocorticoid-induced increases in the fetal hepatic 11β-HSD gene expression and the resultant increase in the C-11 activation index during the last days of fetal life may play a crucial role in fetal organ maturation and in the endocrine mechanisms leading to parturition. Journal of Endocrinology (1994) 143, 121–126

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Induction of renal phosphoenolpyruvate carboxykinase mRNA: suppressive effect of glucose

1989 ◽  
Vol 257 (1) ◽  
pp. F145-F151
Author(s):  
A. S. Pollock
Keyword(s):  
Metabolic Acidosis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Suppressive Effect ◽  
Oral Glucose ◽  
Prolonged Fasting ◽  
Glucose Loading ◽  
Glucose Administration ◽  
Liver And Kidney ◽  
Gluconeogenic Enzyme ◽  
Effect Of Glucose

The mRNA for the important gluconeogenic enzyme phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32) is expressed in liver and kidney. In the kidney, acidosis is a unique and potent stimulus, whereas insulin, the major counterregulatory hormone of gluconeogenesis, has no effect. In this study, we find that oral glucose administration to rats rapidly decreases the abundance of renal PEPCK mRNA by 50–72%. This reduction takes place in normal euglycemic, in insulin-induced hypoglycemic, and in streptozotocin-induced hyperglycemic diabetic animals. The effect of glucose is not seen in the presence of metabolic acidosis, whether induced by NH4Cl or by prolonged fasting. Therefore, it appears that oral glucose loading is a physiological suppressor of renal PEPCK message abundance, although not in acidosis.

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