The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11ß-hydroxysteroid dehydrogenase

1995 ◽  
Vol 18 (7) ◽  
pp. 576-579 ◽  
Author(s):  
M. Lombes ◽  
S. Kenouch ◽  
A. Souque ◽  
N. Farman ◽  
M. E. Rafestin-Oblin ◽  
...  
The Lancet ◽  
1988 ◽  
Vol 332 (8618) ◽  
pp. 986-989 ◽  
Author(s):  
C.R.W. Edwards ◽  
D. Burt ◽  
M.A. Mcintyre ◽  
E.R. De Kloet ◽  
P.M. Stewart ◽  
...  

Endocrinology ◽  
1994 ◽  
Vol 135 (3) ◽  
pp. 834-840 ◽  
Author(s):  
M Lombes ◽  
S Kenouch ◽  
A Souque ◽  
N Farman ◽  
M E Rafestin-Oblin

1991 ◽  
Vol 260 (5) ◽  
pp. F764-F767
Author(s):  
J. L. Yau ◽  
A. D. Van Haarst ◽  
M. P. Moisan ◽  
S. Fleming ◽  
C. R. Edwards ◽  
...  

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) protects nonspecific renal mineralocorticoid receptors from exposure to circulating glucocorticoid in vivo by catalyzing the conversion of corticosterone to inactive 11-dehydrocorticosterone. Although 11 beta-OHSD bioactivity and aldosterone binding sites are found in distal tubular cells, mineralocorticoid receptor and 11 beta-OHSD immunoreactivities are not colocalized. However, there are several kidney isoforms of 11 beta-OHSD, not all of which may be immunoreactive, whereas only a single mRNA species has been described. Using in situ hybridization we found 11 beta-OHSD mRNA is highly expressed in all renal tubular epithelia in the rat. It is therefore likely that 11 beta-OHSD is colocalized with mineralocorticoid receptors in distal tubular cells.


2008 ◽  
Vol 197 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Deborah M Sloboda ◽  
Timothy J M Moss ◽  
Shaofu Li ◽  
Stephen G Matthews ◽  
John R G Challis ◽  
...  

To determine the expression of glucocorticoid metabolizing and action genes in the hippocampus of fetal, neonatal, and adult sheep. Pregnant ewes (or their fetuses) received intramuscular injections of saline or betamethasone (BETA, 0-5 mg/kg) at 104, 111, 118, and/or 125 days of gestation (dG). Hippocampal tissue was collected prior to (75, 84, and 101 dG), during (109 and 116 dG), or after (121, 132, and 146 dG; 6 and 12 postnatal weeks; 3.5 years of age) saline or BETA injections. Hippocampal glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11β-hydroxysteroid dehydrogenase (11βHSD)1 and 11βHSD2 mRNA levels were determined using qRT-PCR. Control animals late in gestation demonstrated a decrease in mRNA encoding GR and 11βHSD1, whereas 11βHSD2 was undetectable, consistent with a damping of the negative feedback influence of circulating or locally produced cortisol on the hypothalamic–pituitary–adrenal (HPA) axis. BETA-administration had transient effects on fetal GR and MR, and early in postnatal life (12 weeks of age) 11βHSD1 mRNA was increased. Hippocampal MR mRNA was elevated in adult offspring exposed to either one or four doses of maternal BETA (P<0.001). Four courses of maternal BETA increased 11βHSD2 (P<0.05) but not 11βHSD1 mRNA levels. Late in gestation a reduction in hippocampal GR and 11βHSD1 mRNA suggests lessening of glucocorticoid negative feedback, facilitating increased preterm HPA activity and parturition. Adult offspring of BETA-treated mothers demonstrated increased MR and 11βHSD2 mRNA, therefore it appears that exposure of fetus to high levels of synthetic glucocorticoids may have long-lasting effects on the hippocampal expression of HPA-related genes into adulthood.


Author(s):  
Shuji Ohno ◽  
Masanori Ohta ◽  
Shizuo Nakajin

Abstract: Glucocorticoid (GC) concentrations in peripheral tissues are precisely regulated by 11β-hydroxysteroid dehydrogenase (HSD) isozymes. When considering the physiological effects of GC in various tissues, quantitative determination of these isozymes and other components involved in corticosteroid signaling is important and informative. We thus performed comprehensive determination of the expression of these mRNAs in a wide range of human tissues.: An absolute comparison of mRNA expression of human 11β-HSD isozymes, hexose-6-phosphate dehydrogenase (H6PDH), glucose-6-phosphate transporter (G6PT), glucocorticoid receptors (GRs), and mineralocorticoid receptor (MR) was performed by real-time RT-PCR.: Human 11β-HSD type 1 mRNA was strongly expressed in the liver and placenta at comparatively high levels. H6PDH was expressed at low copy number, and comparatively high expression was observed in the kidney, testis, and ovary. G6PT expression was ubiquitous, but marked expression was observed in the liver, kidney, small intestine, and colon. GRα was also ubiquitously expressed at relatively high levels, which were approximately 10-fold higher than those of MR, whereas GRβ levels were below the detection limit in all tissues. 11β-HSD type 2 was predominantly expressed in the kidney, small intestine and colon; however, copy numbers of these transcripts showed a nearly identical pattern to type 1. MR was observed in various tissues examined, but was not fully correlated to the distribution of 11β-HSD type 2.: The present quantitative results were partially consistent with previous studies. This quantification method can thus provide valuable information for understanding the physiological effects and physiological roles of glucocorticoid in humans.


1997 ◽  
Vol 82 (11) ◽  
pp. 3859-3863 ◽  
Author(s):  
Gen Hirasawa ◽  
Hironobu Sasano ◽  
Ken-ichi Takahashi ◽  
Kouhei Fukushima ◽  
Takashi Suzuki ◽  
...  

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