Characterization of 11 beta-hydroxysteroid dehydrogenase activity in fetal and adult ovine tissues

1995 ◽  
Vol 7 (3) ◽  
pp. 377 ◽  
Author(s):  
EK Kim ◽  
CE Wood ◽  
M Keller-Wood
Keyword(s):  
Limit Of Detection ◽  
Adult Life ◽  
Hydroxysteroid Dehydrogenase ◽  
Late Gestation ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Optimum Ph ◽  
Kidney Liver ◽  
The Brain

11 Beta-hydroxysteroid dehydrogenase (11 beta-HSD) converts 11-hydroxycorticosteroids to 11-oxocorticosteroids, thereby influencing the availability of bioactive cortisol or corticosterone in target tissues. The activity of this enzyme was investigated in sheep by: (1) measuring relative 11 beta-HSD activities in kidney, liver and placenta, and in various areas of the brain (hypothalamus, hippocampus, and brainstem); (2) characterizing the optimum pH of activities in the tested tissues; (3) investigating the possible effect of gonadal steroids on 11 beta-HSD activity in adult hypothalamus and kidney; and (4) investigating possible developmental changes in activities in the tested tissues. The optimum pH in liver and placenta was pH 9-10, whereas the optimum pH in kidney was pH 7-8. In tissues from adult ewes, 11 beta-HSD activity was highest in liver (84.6 +/- 3.8%) and kidney (49.8 +/- 11.6%), lower but measurable in pituitary (38.8 +/- 3.7%), and near the limit of detection in hypothalamus and hippocampus (2.7 +/- 0.9% and 3.2 +/- 0.8% respectively). Liver, kidney and pituitary from late-gestation fetal sheep contained activities which were similar to those in the adult (76.9 +/- 4.5%, 66.0 +/- 6.7% and 26.3 +/- 3.0% respectively). Activity in the pituitary was not related to fetal gestational age. Placenta also contained measureable 11 beta-HSD activity (21.4 +/- 4.7%). However, no activity was detected in hypothalamus (-1.7 +/- 0.2%), hippocampus (-0.2 +/- 0.6%) or brainstem (-1.0 +/- 0.6%) in late-gestation fetal or neonatal sheep. Enzyme activities in kidney and hypothalamus did not change significantly when the circulating concentrations of ovarian steroids were altered over a 1-3-week period. It is concluded that the ovine kidney, liver and placenta, but not hypothalamus or cerebral cortex, contain 11 beta-HSD activity. In addition, there is no change in 11 beta-HSD activity between late-gestation fetal life and adult life, and the relative activities are not altered by the ovarian steroid milieu.

The lack of impact of peri-implantation or late gestation nutrient restriction on ovine fetal renal development and function

2011 ◽  
Vol 2 (4) ◽  
pp. 236-249 ◽  
Author(s):  
L. M. Braddick ◽  
D. M. Burrage ◽  
J. K. Cleal ◽  
D. E. Noakes ◽  
M. A. Hanson ◽  
...  
Keyword(s):  
Kidney Development ◽  
Adult Life ◽  
Late Gestation ◽  
Fetal Life ◽  
Ang Ii ◽  
Nutrient Requirements ◽  
Fetal Sheep ◽  
Fetal Biometry ◽  
Maternal Undernutrition ◽  
And Function

Unbalanced nutrition during critical windows of development is implicated in determining the susceptibility to hypertension and cardiovascular disease in adult life, but the underlying mechanisms during fetal life have not been fully elucidated. We investigated the effects of moderate nutritional restriction during critical windows in gestation on late gestation fetal sheep growth, cardiovascular and renal renin-angiotensin system function. Ewes were fed 100% nutrient requirements (control), or 40–50% nutrient requirements during the peri-implantation period (1–31 days gestation (dGA), PI40 and PI50), or 50% nutrient requirements in late gestation (104–127 dGA). At 125 ± 2 dGA, fetal cardiovascular and renal function were measured at baseline, and during frusemide, angiotensin II (Ang II), phenylephrine and hypoxia challenges. Maternal undernutrition had no effect on fetal biometry, kidney weight, nephron number, basal cardiovascular function or cardiovascular and renal responses to frusemide. Fetal blood pressure response to Ang II was blunted in PI50 (P< 0.05), but not in PI40 groups. There was no difference between groups in the cardiovascular or endocrine response to hypoxia. The lack of effect of moderate undernutrition within key developmental windows of fetal kidney development on fetal renal structure and function suggests that renal mechanisms do not underlie our previous observations of cardiovascular dysfunction in adulthood following early-life undernutrition.

Distribution of calbindin-D28K in the brain of the fetal sheep in late gestation

1995 ◽  
Vol 675 (1-2) ◽  
pp. 303-315 ◽  
Author(s):  
T.J. McDonald ◽  
C. Li ◽  
R.H. Wasserman
Keyword(s):  
Late Gestation ◽  
Fetal Sheep ◽  
Calbindin D28k ◽  
The Brain

scholarly journals Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth

2004 ◽  
Vol 63 (3) ◽  
pp. 405-412 ◽  
Author(s):  
I. C. McMillen ◽  
B. S. Muhlhausler ◽  
J. A. Duffield ◽  
B. S. J. Yuen
Keyword(s):  
Adipose Tissue ◽  
Fat Mass ◽  
Maternal Nutrition ◽  
Adult Life ◽  
Later Life ◽  
Late Gestation ◽  
Relative Mass ◽  
Moderate Increase ◽  
Fetal Life ◽  
Fat Depots

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the ‘unilocular’ component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a ‘lipostatic’ role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

scholarly journals Genomic Effect of Triclosan on the Fetal Hypothalamus: Evidence for Altered Neuropeptide Regulation

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2686-2697 ◽  
Author(s):  
Maria Belen Rabaglino ◽  
Eileen I. Chang ◽  
Elaine M. Richards ◽  
Margaret O. James ◽  
Maureen Keller-Wood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Fetal Brain ◽  
Late Gestation ◽  
Gene Set Enrichment Analysis ◽  
Postnatal Life ◽  
Fetal Life ◽  
Low Doses ◽  
Fetal Sheep ◽  
Reproductive Process

Triclosan (TCS), an antibacterial compound commonly added to personal care products, could be an endocrine disruptor at low doses. Although TCS has been shown to alter fetal physiology, its effects in the developing fetal brain are unknown. We hypothesize that exposure to TCS during fetal life could affect fetal hypothalamic gene expression. The objective of this study was to use transcriptomics and systems analysis to identify significantly altered biological processes in the late gestation ovine fetal hypothalamus after direct or indirect exposure to low doses of TCS. For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n = 4) or TCS (250 μg/d; n = 4) iv. For indirect TCS exposure, TCS (100 μg/kg · d; n = 3) or vehicle (n = 3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured through microarray. Hierarchical clustering of all samples according to gene expression profiles showed that samples from the TCS-treated animals clustered apart from the controls. Gene set enrichment analysis revealed that fetal hypothalamic genes stimulated by maternal and fetal TCS infusion were significantly enriching for cell cycle, reproductive process, and feeding behavior, whereas the inhibited genes were significantly enriching for chromatin modification and metabolism of steroids, lipoproteins, fatty acids, and glucose (P &lt; .05). In conclusion, short-term infusion of TCS induces vigorous changes in the fetal hypothalamic transcriptomics, which are mainly related to food intake pathways and metabolism. If these changes persist to postnatal life, they could result in adverse consequences in adulthood.

Impact of chronic hypoxemia on blood flow to the brain, heart, and adrenal gland in the late-gestation IUGR sheep fetus

2015 ◽  
Vol 308 (3) ◽  
pp. R151-R162 ◽  
Author(s):  
Rajan Poudel ◽  
I. Caroline McMillen ◽  
Stacey L. Dunn ◽  
Song Zhang ◽  
Janna L. Morrison
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Adrenal Gland ◽  
Temporal Lobe ◽  
Late Gestation ◽  
Control Group ◽  
Surgical Removal ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
The Brain

In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational PaO2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation.

scholarly journals The late gestation increase in circulating ACTH and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombinant ovine leptin

2002 ◽  
Vol 174 (2) ◽  
pp. 259-266 ◽  
Author(s):  
DC Howe ◽  
A Gertler ◽  
Keyword(s):  
Late Gestation ◽  
Calorie Intake ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Fetal Circulation ◽  
Intracerebroventricular Infusion ◽  
Energy Stores ◽  
Neuroendocrine Responses ◽  
Plasma Leptin ◽  
Sheep Fetus

The obese gene product leptin, originally characterised as an adipocyte hormone coordinating the behavioural and neuroendocrine responses to starvation, is expressed in fetal adipocytes and placental trophoblast cells and is present in the fetal circulation. Concentrations of leptin in fetal blood correlate with fetal bodyweight and fat mass. In post-natal life, leptin conveys information about calorie intake and the state of adipose tissue energy stores, and plasma leptin levels are generally inversely correlated with hypothalamo-pituitary adrenal (HPA) activity. Late fetal life is characterised by increasing HPA activity that prepares the fetus for extrauterine life and initiates the endocrine cascade leading to parturition. We have investigated the hypothesis that leptin in the fetal circulation can inhibit the fetal HPA axis, thereby providing a mechanism by which the fetus can determine the fine timing of parturition as long as it is adequately nourished and growing appropriately. Here we show that a 5-day intracerebroventricular infusion of leptin to the sheep fetus in late gestation inhibits the pre-parturient rise in ACTH and cortisol concentrations, and that this seems to be a centrally mediated effect.

scholarly journals Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

2012 ◽  
Vol 34 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Tamara Yawno ◽  
Margie Castillo-Melendez ◽  
Graham Jenkin ◽  
Euan M. Wallace ◽  
David W. Walker ◽  
...  
Keyword(s):  
Late Gestation ◽  
Fetal Sheep ◽  
The Brain

scholarly journals 043. Role of TGFβ in adrenal steroidogenesis before birth

2004 ◽  
Vol 16 (9) ◽  
pp. 43
Author(s):  
C. L. Coulter
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hepatic Glucose Production ◽  
Mammalian Species ◽  
Late Gestation ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Adrenal Steroidogenesis ◽  
Metabolic Systems

During mammalian development there are periods when the fetal adrenal is either relatively refractory or increasingly sensitive to trophic stimulation. This pattern of regulation of adrenal growth and function ensures that the fetal lungs, liver, brain and kidney are exposed in a programmed temporal sequence to the genomic actions of circulating glucocorticoids. A range of studies in the rat and sheep have also demonstrated that exposure to excess glucocorticoids at inappropriate times in fetal life inhibits fetal growth and permanently reprograms the development of the cardiovascular and metabolic systems resulting in postnatal hypertension, abnormal hepatic glucose production and poor glucose tolerance In most mammalian species, there are therefore a range of mechanisms that protect the fetus from exposure to glucocorticoids of either maternal or fetal origin at inappropriate times in gestation. The factors that act to maintain periods of adrenal quiescence are not known. There is evidence that intra-adrenal transforming growth factor beta 1 (TGFβ1) is an inhibitor of adrenocortical steroidogenesis in the adult. In recent studies, we have demonstrated that expression of TGFβ1 is high in the fetal sheep adrenal at around 100�days gestation and that adrenal TGFβ1 expression then falls with increasing gestational age and is lowest immediately after birth. Following the activation of adrenal cytochrome P450 C17 (CYP17), there is an inverse relationship between adrenal TGFβ1 and CYP17 expression and TGFβ1 may therefore play a novel inhibitory role in the regulation of adrenal steroidogenesis during mid and late gestation. Whilst functional activation of the fetal adrenal is dependent on the fetal hypothalamo–pituitary axis, adrenal TGFβ1 mRNA expression is not altered by disconnection of the fetal hypothalamus and pituitary in late gestation. It therefore appears unlikely that TGFβ1 mRNA expression is regulated directly by either bioactive ACTH or cortisol in late gestation. The mechanism by which TGFβ1 expression is upregulated in mid gestation remains to be determined.

scholarly journals Aldosterone in the brain

2009 ◽  
Vol 297 (3) ◽  
pp. F559-F576 ◽  
Author(s):  
Joel C. Geerling ◽  
Arthur D. Loewy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Hydroxysteroid Dehydrogenase ◽  
Solitary Tract ◽  
Barrier Penetration ◽  
The Central Nervous System ◽  
The Brain

Pharmacological and physiological phenomena suggest that cells somewhere inside the central nervous system are responsive to aldosterone. Here, we present the fundamental physiological limitations for aldosterone action in the brain, including its limited blood-brain barrier penetration and its substantial competition from glucocorticoids. Recently, a small group of neurons with unusual sensitivity to circulating aldosterone were identified in the nucleus of the solitary tract. We review the discovery and characterization of these neurons, which express the enzyme 11β-hydroxysteroid dehydrogenase type 2, and consider alternative proposals regarding sites and mechanisms for mineralocorticoid action within the brain.

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