11β-Hydroxysteroid dehydrogenase in developing rat intestine

1996 ◽  
Vol 148 (3) ◽  
pp. 561-566 ◽  
Author(s):  
J Pácha ◽  
I Mikšík

Abstract The enzyme 11β-hydroxysteroid dehydrogenase (11β-OHSD) prevents the binding of corticosterone to mineralocorticoid receptors by reversible conversion of biologically active corticosterone to inactive 11-dehydrocorticosterone. To clarify the relationship between high plasma concentrations of corticosterone during weaning and high activity of intestinal transport pathways that are induced by aldosterone in immature intestine, we have studied the distribution, developmental pattern and regulation of 11 β-OHSD in intestinal segments that possess mineralocorticoid target epithelium. Dehydrogenase activity was already high in the caecum, and the proximal and distal colon on the second postnatal day and altered little until adulthood. In contrast, the activity in the ileum was low during the first two weeks of life, rose more than 5-fold in the next 20 days to attain a peak in 30-day-old rats, and thereafter declined to the values of adult animals. There was no significant reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) in any intestinal segment of young and adult rats. The regulation of intestinal 11β-OHSD by corticosteroids and thyroid hormones was studied in the ileum and distal colon. In weanling rats, adrenalectomy or a high-salt diet decreased 11β-OHSD activities in both intestinal segments whereas dexamethasone administration prevented this decline in adrenalectomized rats and administration of deoxycorticosterone acetate led to a significant increase of intestinal 11β-OHSD activities in rats kept on a high-salt diet. Dexamethasone administration to intact adult rats also stimulated 11 β-OHSD activity in the ileum and distal colon. The changes in thyroid status of weanling rats did not change the 11β-OHSD activities. We conclude that (1) the developmental patterns of 11β-OHSD activity in the small and large intestine are not identical and this discrepancy may facilitate the maturation effect of glucocorticoids in the small intestine and the stimulatory effect of aldosterone in the large intestine and (2) corticosteroids but not thyroid hormones can modulate 11β-OHSD activity in the developing intestine. Journal of Endocrinology (1996) 148, 561–566

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yoshiyu Takeda ◽  
Yoshimichi Takeda ◽  
Shigehiro Karashima ◽  
Mitsuhiro Kometani ◽  
Atsushi Hashimoto ◽  
...  

Abstract ENDO 2020 Epigenetic regulation of 11beta-hydroxysteroid dehydrogenase 1 and 2 gene in salt-sensitive hypertensive rats [Objective]11Beta-hydroxysteroid dehydrogenase type1 (11-HSD1) is the modulator of glucocorticoid hormone and type2 (11-HSD2) is the modulator of mineralocorticoid hormone. We investigated the effect of high salt diet on the methylation of both enzyme gene in salt-sensitive hypertensive (SSH) rats [Methods]SSH rats were fed a high (7% NaCl) or normal (0.45%) salt chow for 4 weeks. Body weight, blood pressure, plasma and urinary aldosterone concentration and PRA were measured. DNA was extracted from kidneys and visceral fats. Bisulfite sequencing and Pyrosequencing were done for the analysis of methylation status of 11-HSD1 and 2 gene. [Results] High salt diet significantly decreased methylation ratio of 11-HSD1 gene in the visceral fats of SSH rats compared with controls (p<0.05). The methylation ratio of 11-HSD2 gene in the kidney of SSH rats was not influenced by high salt diet. [Discussion and Conclusion]11-HSD1 overexpression in visceral fats in mice was reported to show SSH. We reported decreased 11-HSD2 activity in the artery in SSH rats. In this study high salt diet affected methylation status of 11-HSD1 in the adipose tissue but not 11-HSD2 gene in the kidney in SSH. Food intake such as salt may influence the epigenesis of 11-HSD and induce hypertension.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Nauilo Lima Costa ◽  
Débora Rothstein Ramos ◽  
Karen Lucasechi Lopes ◽  
Luzia Naoko Shinohara Furukawa ◽  
Joel Claudio Heimann

1998 ◽  
Vol 275 (6) ◽  
pp. G1317-G1323 ◽  
Author(s):  
M. Augusta Vieira-Coelho ◽  
Vera A. Lucas Teixeira ◽  
Yigael Finkel ◽  
Patricio Soares-Da-Silva ◽  
Alejandro M. Bertorello

During high-salt diet endogenous dopamine (DA) reduces jejunal sodium transport in young but not in adult rats. This study was designed to evaluate whether this effect is mediated, at the cellular level, by inhibition of Na+-K+-ATPase activity. Enzyme activity was determined in isolated jejunal cells by the rate of [γ-32P]ATP hydrolysis. Cells were obtained from weanling and adult rats fed either with high- or normal-salt diet. In 20-day-old but not in 40-day-old rats Na+-K+-ATPase activity was significantly reduced during high-salt diet. This inhibition was abolished by a blocker of DA synthesis. The decreased activity was associated with a decreased α1-subunit at the plasma membrane. During high-salt diet there was an increase in DA content in jejunal cells from 20-day-old rats, associated with a parallel decrease in 5-hydroxytryptamine, compared with normal-salt diet. In 40-day-old rats, however, the catecholamine level remained unchanged during high-salt diet. Incubation of isolated jejunal cells with DA resulted in a dose-dependent inhibition of Na+-K+-ATPase activity in 20- but not in 40-day-old rats. We conclude that during high-salt diet, jejunal Na+-K+-ATPase in 20-day-old rats is inhibited, and this effect is likely to be mediated by locally formed DA.


Steroids ◽  
2009 ◽  
Vol 74 (12) ◽  
pp. 978-982 ◽  
Author(s):  
Mikiya Usukura ◽  
Aoshuang Zhu ◽  
Takashi Yoneda ◽  
Shigehiro Karashima ◽  
Kunimasa Yagi ◽  
...  

1994 ◽  
Vol 107 (3) ◽  
pp. 675-679 ◽  
Author(s):  
Yigael Finkel ◽  
Ann Christine Eklöf ◽  
Lena Granquist ◽  
Patricio Soares-da-Silva ◽  
Alejandro M Bertorello

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 463-P
Author(s):  
TOMONORI KIMURA ◽  
YOSHITAKA HASHIMOTO ◽  
TAKAFUMI SENMARU ◽  
EMI USHIGOME ◽  
MASAHIDE HAMAGUCHI ◽  
...  
Keyword(s):  

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.


Hypertension ◽  
2005 ◽  
Vol 45 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Magdalena Gonzalez ◽  
Lorena Lobos ◽  
Felipe Castillo ◽  
Lorna Galleguillos ◽  
Nandy C. Lopez ◽  
...  

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