| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Articles |
Laboratory of Molecular Hypertension (R.E.S., K.X.Z.L., Z.K.) and Vascular Biology Laboratory (R.K.A.), Baker Medical Research Institute, Prahran, Australia
Address all correspondence and requests for reprints to: Dr. Zygmungt Krozowski, Baker Medical Research Institute, P.O. Box 348, Prahran, Victoria 3181, Australia.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In frozen sections of rat kidney, strong staining was seen with the RAH23 antibody in the distal tubule; weaker staining was observed in the thick ascending loop of Henle and the medullary and papillary collecting ducts. Punctate cortical staining was observed in the fetus at 20 days gestation and in 8-day-old rats, with a noticeable increase in the staining pattern at 16 days of age. The kidney did not attain the adult pattern of staining until 28 days of age. Epithelia of ileum and colon also stained with RAH23, as did excretory ducts of the submandibular gland. Intrahepatic and excretory bile ducts displayed strong immunoreactivity in the epithelial lining. Rat adrenal glands showed evidence of the 11ßHSD2 antigen in the zona fasciculata and zona reticularis, but not in the zona glomerulosa or medulla.
Western blot analysis with the RAH23 antibody revealed strong bands in the kidney, colon, adrenal gland, and submandibular gland at 40 kDa, colinear with the migration of the cloned 11ßHSD2 enzyme. A band of medium intensity was also seen at this size in the pancreas, whereas a band of moderate intensity was seen in the bile duct, and weaker bands were noticed in the stomach, small intestine, and liver, with a diffuse band at 36–42 kDa in the prostate. Strong bands were seen in the pancreas and prostate at 78 kDa, with weaker signals in the colon, adrenal, stomach, and bile duct. A number of tissues also displayed multiple bands at about 30 kDa. Enzymatic assays on tissue homogenates showed extensive conversion of corticosterone to its 11-dehydro product in an NAD-dependent manner in the submandibular gland, adrenal gland, and kidney, but not in the pancreas or prostate.
This study confirms the ubiquitous presence of 11ßHSD2 in sodium-transporting epithelia, demonstrates the high level of 11ßHSD2 protein and enzyme activity in the rat adrenal, and suggests a possible role for the enzyme in the biliary system. Further studies are required to determine the relevance of the various molecular species to the activity, latency, and processing of the enzyme.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In a recent study we showed that 11ßHSD2 is present in nonrenal sodium-transporting epithelia such as those in the sweat gland, salivary gland, and gastrointestinal tract, suggesting that a single isoform is responsible for endowing mineralocorticoid specificity in man (8). In situ studies in the rat have also demonstrated message in a range of nonmineralocorticoid target tissues, including specific areas of the brain not known to contain mineralocorticoid receptors (9, 10). The unavailability of an antibody against the rat 11ßHSD2 antigen has precluded immunohistochemical and molecular studies of the protein in the rat. In the present study we localized the 11ßHSD2 protein in a range of peripheral rat tissues and characterized its molecular forms by Western blot analysis using a newly developed monospecific polyclonal antibody raised against the nonconserved C-terminal peptide of the rat 11ßHSD2 protein (11, 12).
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Tissue collection
Rat tissues were obtained from male Sprague-Dawley rats. Rats
were killed after rendering them unconscious in a CO2
chamber. Tissues were removed and either snap-frozen in liquid nitrogen
or embedded in Tissue-Tek OCT embedding medium (Miles, Elkhart, IN),
frozen in liquid nitrogen, and stored at -70 C until needed.
Immunohistochemical studies
Frozen tissues were cut into 6-µm sections, layered on
gelatin-coated slides, and fixed in 4% paraformaldehyde solution. A
three-layer immunoperoxidase technique of immunostaining was performed
as previously described (13). The immunopurified primary antibody RAH23
was used at concentrations of 1–2.5 µg/ml on all tissues. The
control antiserum was a solid phase absorbed rabbit IgG fraction from
healthy nonimmunized animals (Dako Laboratories, Carpenteria, CA) and
was used at 2.5 µg/ml. Tissue sections were counterstained with
hematoxylin for 2 min. Photography was performed using a Weild Leitz
microphotography system (Leitz, Rockleigh, NJ).
Preparation of microsomal fractions
Rat tissues were collected from male rats and frozen immediately
in liquid nitrogen. Homogenates were prepared by homogenization in 4
vol homogenizing buffer (0.25 M sucrose, 10 mM
sodium phosphate, and 1 mM phenylmethylsulfonylfluoride, pH
7.4) in an Ika-Ultraturrex T25 homogenizer (Janke and Kunkle, Stauten,
Germany). The microsomal fraction was prepared from homogenates by
centrifugation (1,500 x g for 5 min at 4 C) followed
by a high speed centrifugation of the supernatant at 100,000 x
g for 60 min at 4 C. Microsomes were resuspended in
homogenizing buffer, and aliquots of 0.5 ml were stored at -70 C until
required. Chinese hamster ovary cells transfected with papilloma virus
cells (14, 15) were transfected with the rat expression plasmid pRHSD2,
and microsomes were prepared as previously described (11).
Western blot analysis
Microsomal proteins (50 µg) were separated by 5–15% SDS-PAGE
gradient gel electrophoresis under reducing conditions and transferred
to nitrocellulose filters (Scheicher and Schuell, Darmstadt, Germany)
for 2 h on ice. After blocking nonspecific sites, the
nitrocellulose blot was incubated overnight at 4 C with the
immunopurified RAH23 polyclonal antibody at a concentration of 1
µg/ml in the presence of 0.5% skimmed milk powder in PBS, pH 7.4,
containing 0.1% Tween-20. The filter was then incubated at room
temperature for 60 min with a 1:5000 dilution of goat antirabbit IgG
antibody conjugated to horseradish peroxidase. The blots were washed in
PBS-0.1% Tween-20 for 60 min before revelation using an
chemiluminescent kit (DuPont-New England Nuclear, Boston, MA) according
to the manufacture’s instructions.
Enzymatic analysis
Tissue samples were homogenized in 4 vol homogenizing buffer
(0.25 M sucrose, 140 mM KCl, 10 mM
sodium phosphate, and 1 mM phenylmethylsulfonylfluoride, pH
7.6). 11ßHSD2 activity in homogenates was determined by measuring the
conversion of [3H]corticosterone to
[3H]11-dehydrocorticosterone. Incubations were performed
in a total volume of 500 µl homogenizing buffer with 2 nM
[3H]corticosterone and 10 nM unlabeled
corticosterone in the presence or absence of 500 µM
NAD+ at 37 C for 10–60 min. Homogenates were added at a
protein concentration of 600 µg/ml for kidney and adrenal and 1 mg/ml
for prostate, pancreas, and submandibular gland. The reaction was
stopped, and the steroid was extracted by the addition of 3 vol ethyl
acetate. Separation of steroids was performed using TLC with silica gel
plates (Merck, Darmstadt, Germany) in a chloroform-ethanol (92:8)
system.
Determination of protein
Protein concentration was determined colorimetrically by the
Bradford method using Bio-Rad protein dye (Richmond, CA) and
calibration against standards of 
-globulin (16).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). The cellular morphology of the latter tubules
resembles that of the thick ascending loop of Henley. Staining was also
present in collecting ducts of the medulla (Fig. 1B) and extended into
the horns of the papilla, with the proximal portion of the papilla
showing more tubular staining than the distal part (Fig. 1C). The
specificity of the antibody was confirmed using nonimmune serum (Fig. 1D). In a series of developmental studies on the kidney, we observed
RAH23 staining of renal tubules in the fetus at 20 days gestation (Fig. 2A), with little change in the staining pattern 8 days
postpartum (Fig. 2B). There was a noticeable increase in the number of
tubules staining at 16 days of age (Fig. 2C), and the adult staining
pattern was achieved by 28 days of age (Fig. 2D).
|
|
), and the
specificity of staining could be confirmed by treatment with nonimmune
serum (Fig. 3B). In the gastrointestinal tract, specific staining for
11ßHSD2 was seen in the enterocytes of the ileum and the goblet
cells, but not in the lamina propria (Fig. 4, A and B).
In the distal colon, absorptive cells of the surface epithelium and
crypts of Lieberkuhn also showed specific staining (Fig. 4, C and
D).
|
|
, A and B) and the
excretory bile duct (Fig. 5C). The RAH23 antibody also specifically
stained the zona reticularis and zona fasciculata regions of the
adrenal gland, but not the zona glomerulosa or medulla (Fig. 6, A and B). Faint staining of ductal elements was also
seen in the pancreas, whereas the vasculature, lung, and prostate did
not stain (results not shown).
|
|
). A strong signal was observed at 40 kDa in
Chinese hamster ovary cells transfected with papilloma virus cells
transfected with the rat 11ßHSD2 clone and in the kidney, colon,
adrenal, submandibular gland, and pancreas. Significant amounts of the
40-kDa species were detected in the bile duct, and weaker bands were
seen in the stomach, small intestine, and liver. A diffuse band was
observed in the prostate between 36–42 kDa, but there was no
detectable band of similar size in the aorta or lung. A strong band was
seen in the pancreas, prostate, and stomach at 78 kDa, with weaker
bands in bile duct, colon, adrenal gland, and liver. Several tissues
also showed multiple bands at about 30 kDa, with the strongest signals
present in the colon and pancreas. Only in the aorta and lung did there
appear to be no bands at either 40 or 78 kDa, although a weak signal
was detected in both tissues at 30 kDa.
|
shows that in
homogenates of kidney, adrenal glands, and submandibular glands, enzyme
activity is significantly increased by the addition of NAD, consistent
with the presence of the 11ßHSD2 enzyme, whereas prostate and
pancreas displayed no detectable activity.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The 11ßHSD2 enzyme has previously been localized in high amounts in classical sodium-transporting epithelia, the ileum and term placenta in humans (8, 13, 17, 18), but studies in the rat have been limited to the detection of message (19, 20). In humans, lower levels of immunostaining were also detected in the thick ascending limb of the loop of Henle (13, 17). In the present study, 11ßHSD2 was also detected in the thick ascending limb of the loop of Henle. In this part of the nephron, sodium is reabsorbed by a mechanism coupled to chloride retention without concomitant potassium secretion, with aldosterone modulating ion transport (21). Isolated segments of thick ascending limb have been shown to possess significant amounts of 11ßHSD2 activity (22), suggesting that this segment is a mineralocorticoid target.
The proximal papillary collecting duct was also shown to contain low levels of 11ßHSD2 immunoreactivity, and mineralocorticoid receptors have been detected in this part of the nephron (23), although it is unresolved whether aldosterone stimulates sodium reabsorption here. The 11ßHSD2 enzyme could play a role in modulating the glucocorticoid enhancement of antidiuretic hormone-dependent water permeability in the papillary collecting duct (24). Message for 11ßHSD1 has also been detected in the rat papilla (25, 26), although the directionality of 11ßHSD1 enzyme activity is not known.
Developmental studies showed the presence of low numbers of 11ßHSD2-positive tubules in the fetal rat kidney cortex before birth, with the rat attaining the adult staining pattern sometime between 16–28 days of age. Studies in other species have provided evidence for fetal 11ßHSD2 activity, with highest amounts in the kidney (27), whereas in the mouse, renal 11ßHSD2 mRNA is present by 13 days gestation, preceding the appearance of message for mineralocorticoid receptor (28). The developmental pattern of staining observed in our study parallels the maturation of the distal tubule, which is not complete until the fourth week of life. Weaning is initiated by 14–15 days of age, is usually complete by 21 days, and is accompanied by a surge in serum corticosterone and thyroid hormone levels that complete maturation of the nephron (29).
Salivary gland ducts demonstrate changes in sodium flux in response to mineralocorticoids. The rat submandibullar gland showed 11ßHSD2 staining along collecting ducts, colocalizing the enzyme with the pattern of mineralocorticoid receptor distribution in the rat (30). The degree to which decreased 11ßHSD2 activity leads to the increase in salivary mineralocorticoid action in some hypertensive rat models (31) is currently unknown.
Our localization studies in the rat gastrointestinal tract produced a distribution identical to that obtained in human tissues, with the majority of the epithelial cells of the ileum and colon staining with the RAH23 antibody. The ileum possesses receptors for the absorption of bile salts, and the 11ßHSD2 enzyme may be part of the mechanism facilitating enterohepatic circulation, although high concentrations of bile acids and their amidates are known to inhibit 11ßHSD2 activity (32). In the colon, 11ßHSD2 colocalizes with the mineralocorticoid receptor (30) and serves to endow aldosterone specificity, facilitating the absorption of sodium. The 11ßHSD1 enzyme is also present in rat colon, but appears restricted to the lamina propria (33). Recently, evidence has been presented for a novel corticosteroid receptor that binds 11-dehydrocorticosterone in rat colon (34) and possibly vascular smooth muscle cells (35). The 11ßHSD2 enzyme is likely to play a pivotal role in modulating the levels of ligand for this binding site.
A surprising finding of the present study was the identification of 11ßHSD2 in the epithelium of intrahepatic and excretory bile ducts, with evidence for its presence in the latter coming from both immunohistochemical and Western blot analysis. The bile duct and gall bladder absorb water to concentrate bile fluid (36), but this process is not known to be mediated by mineralocorticoids. Message for 11ßHSD2 has been described in the bile duct of the fetal mouse, but not in the adult (28). The role of 11ßHSD2 in the biliary system could be to metabolize glucocorticoids or one or more compounds absorbed from the bile fluid during its passage to the duodenum. In this context it is important to note that recent studies have demonstrated potent reductive metabolism of dexamethasone by 11ßHSD2 (37), suggesting new roles and substrates for the enzyme.
The 11ßHSD2 enzyme was also found to be present in the adrenal gland in large amounts. Previous studies have demonstrated abundant message in the sheep and rat adrenal (11, 12, 38), although it was not detected in the mouse (39). Message has been localized to the zona fasciculata and zona reticularis in the sheep (40) and rat (10), consistent with localization of the rat 11ßHSD2 antigen in the present study. The role of 11ßHSD2 in the adrenal gland may be to protect cells from excessive levels of glucocorticoid and to modulate the production of active hormone. A perinuclear localization of the enzyme would allow simultaneous production of corticosterone and protection of the cell from glucocorticoid toxicity. Recently, evidence has been provided for just such a localization in transfected cells using a fluorescent fusion protein (41).
The cloned rat 11ßHSD2 enzyme has a predicted molecular size of 43,721 daltons (12), but was found by Western blot analysis to migrate as a 40-kDa species. A similar underestimation of size has been reported for the human enzyme in both tissue extracts and in vitro translation studies (13, 18) and may reflect the presence of extensive hydrophobic regions. Western blot studies also showed strong bands in a number of tissues at 78 kDa; this is possibly the result of dimerization or posttranslational modification of the 40-kDa species and could be integral to the phenomenon of latency or enzyme turnover (42). Multiple species have also been observed in immunohistochemical studies of the 11ßHSD1 enzyme (43). It would appear that the 78-kDa species is not enzymatically active, as we failed to detect 11ßHSD2 activity in the pancreas and prostate, two tissues with strong bands at this size. The multiple bands detected at 30 kDa could be N-terminal degradation products, as they are strongest in those tissues with abundant 40- and 78-kDa species. If the 30-kDa species does indeed represent degraded 11ßHSD2, then the weak signals observed in the aorta and lung suggest the presence of small amounts of enzyme in these tissues. Indeed, the detection of bands in most tissues may reflect a common localization, such as in vascular smooth muscle cells, where a previous study in man has shown significant 11ßHSD2 by immunohistochemistry (13). Our inability to observe vascular staining in any of the tissues in the present study could be due to the low level of antigen present per cell, a limitation that appears to be overcome by the concentrating effect of SDS-PAGE.
Although we were unable to demonstrate 11ßHSD2 activity and observed only faint ductal immunohistochemical staining in the pancreas, Western blot analysis showed a band consistent with the presence of the 11ßHSD2 protein. Proteolytic degradation would appear to be the most likely reason for our inability to detect activity and immunostaining, and this is supported by the large amount of the putative degradation product at 30 kDa. The presence of 11ßHSD2 message (15) and mineralocorticoid receptor (44) in the human pancreas suggests that mineralocorticoids may modulate the epithelial sodium channel in pancreatic ducts, the inactivation of which leads to abnormalities in exocrine gland secretion (45).
Despite our inability to detect RAH23 staining and enzymatic activity in the rat prostate, we did observe a broad band on Western blots not inconsistent with the presence of 11ßHSD2. It is possible that posttranslational modification masked the epitope in the immunohistochemical studies and also suppressed the activity of the enzyme. Normal human prostatic cells express message (15) for 11ßHSD2 and metabolize cortisol (46), whereas LNCaP cells appear to contain the mineralocorticoid receptor and both 11ßHSD1 and 11ßHSD2 isoforms (43, 47). The prostate may also metabolize 11ß-hydroxyandrostenedione, an androgen secreted from the adrenals after stimulation with ACTH (48) and previously shown to serve as a substrate for 11ßHSD2 (49).
The present work in the rat complements recent immunohistochemical studies in humans (8, 13, 17). In general, all human and rat mineralocorticoid target tissues contain the 11ßHSD2 enzyme, obviating the need for additional tissue-specific isoforms to endow mineralocorticoid specificity. Currently, little is known about the modulation of 11ßHSD2 activity, although recent studies suggest that it could be regulated by the protein kinase A pathway (50) and via corticosteroids (12). It seems likely that tissue-specific dysregulation of 11ßHSD2 activity is a cause of some pathological conditions, and our present study may aid in the development of certain rat models of disease.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received September 5, 1996.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  J. Goto, F. Otsuka, M. Yamashita, J. Suzuki, H. Otani, H. Takahashi, T. Miyoshi, Y. Mimura, T. Ogura, and H. Makino Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E904 - E916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Usa, R. J. Singh, B. C. Netzel, Y. Liu, H. Raff, and M. Liang Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F186 - F192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Naray-Fejes-Toth and G. Fejes-Toth Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2-expressing cells Am J Physiol Renal Physiol, January 1, 2007; 292(1): F486 - F494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Yao, R. C. Harris, and M.-Z. Zhang Interactions between 11{beta}-hydroxysteroid dehydrogenase and COX-2 in kidney Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1767 - R1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Sher, H. W. Woitge, D. J. Adams, G. A. Gronowicz, Z. Krozowski, J. R. Harrison, and B. E. Kream Transgenic Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Osteoblasts Reveals an Anabolic Role for Endogenous Glucocorticoids in Bone Endocrinology, February 1, 2004; 145(2): 922 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Z. Zhang, S.-w. Wang, H. Cheng, Y. Zhang, J. A. McKanna, and R. C. Harris Regulation of renal cortical cyclooxygenase-2 in young rats Am J Physiol Renal Physiol, November 1, 2003; 285(5): F881 - F888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Gomez-Sanchez, V. Ganjam, Y. J. Chen, Y. Liu, M. Y. Zhou, C. Toroslu, D. G. Romero, M. D. Hughson, A. de Rodriguez, and C. E. Gomez-Sanchez Regulation of 11{beta}-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E272 - E279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Waddell, S. Hisheh, Z. S. Krozowski, and P. J. Burton Localization of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in the Male Reproductive Tract Endocrinology, July 1, 2003; 144(7): 3101 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suzuki, K. Koyama, A. Darnel, H. Ishibashi, S. Kobayashi, H. Kubo, T. Suzuki, H. Sasano, and Z. S. Krozowski Dexamethasone Upregulates 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in BEAS-2B Cells Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1244 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Good, T. George, and B. A. Watts III Aldosterone inhibits HCO-3 absorption via a nongenomic pathway in medullary thick ascending limb Am J Physiol Renal Physiol, October 1, 2002; 283(4): F699 - F706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Woitge, J. R. Harrison, A. Ivkosic, Z. Krozowski, and B. E. Kream Cloning and in Vitro Characterization of {{alpha}}1(I)-Collagen 11{{beta}}-Hydroxysteroid Dehydrogenase Type 2 Transgenes as Models for Osteoblast-Selective Inactivation of Natural Glucocorticoids Endocrinology, March 1, 2001; 142(3): 1341 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Biller, R. J. Unwin, and D. G. Shirley Distal tubular electrolyte transport during inhibition of renal 11{beta}-hydroxysteroid dehydrogenase Am J Physiol Renal Physiol, January 1, 2001; 280(1): F172 - F179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Sheppard, S. Hourigan, K. X. Z. Li, and Z. S. Krozowski Novel nuclear corticosteroid binding in rat small intestinal epithelia Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G536 - G542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Reilly and D. H. Ellison Mammalian Distal Tubule: Physiology, Pathophysiology, and Molecular Anatomy Physiol Rev, January 1, 2000; 80(1): 277 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Sheppard, K. X. Z. Li, and D. J. Autelitano Corticosteroid receptors and 11beta -hydroxysteroid dehydrogenase isoforms in rat intestinal epithelia Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G541 - G547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Nussdorfer, G. P. Rossi, L. K. Malendowicz, and G. Mazzocchi Autocrine-Paracrine Endothelin System in the Physiology and Pathology of Steroid-Secreting Tissues Pharmacol. Rev., September 1, 1999; 51(3): 403 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kato, H. Sasano, S. Ohara, H. Sekine, S. Mochizuki, T. Mune, K. Yasuda, H. Nagura, T. Shimosegawa, T. Toyota, et al. Coexpression of Mineralocorticoid Receptors and 11{beta}-Hydroxysteroid Dehydrogenase 2 in Human Gastric Mucosa J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2568 - 2573. [Abstract] [Full Text]
|
|
|
|
|
|
G. Hirasawa, H. Sasano, T. Suzuki, J. Takeyama, Y. Muramatu, K. Fukushima, N. Hiwatashi, T. Toyota, H. Nagura, and Z. S. Krozowski 11{beta}-Hydroxysteroid Dehydrogenase Type 2 and Mineralocorticoid Receptor in Human Fetal Development J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1453 - 1458. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Mazzocchi, G. P. Rossi, G. Neri, L. K. Malendowicz, G. Albertin, and G. G. Nussdorfer 11ß-Hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex FASEB J, November 1, 1998; 12(14): 1533 - 1539. [Abstract] [Full Text]
|
|
|
|
|
|
D. Fuster, G. Escher, B. Vogt, D. Ackermann, B. Dick, B. M. Frey, and F. J. Frey Furosemide Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Endocrinology, September 1, 1998; 139(9): 3849 - 3854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Sheppard, K. Khoo, Z. S. Krozowski, and K. X. Z. Li Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11beta HSD Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E124 - E131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Naray-Fejes-Toth and G. Fejes-Toth Extranuclear Localization of Endogenous 11{beta}-Hydroxysteroid Dehydrogenase-2 in Aldosterone Target Cells Endocrinology, June 1, 1998; 139(6): 2955 - 2959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Burton, Z. S. Krozowski, and B. J. Waddell Immunolocalization of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in Rat Uterus: Variation Across the Estrous Cycle and Regulation by Estrogen and Progesterone Endocrinology, January 1, 1998; 139(1): 376 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Brem, R. B. Bina, T. C. King, and D. J. Morris Localization of 2 11{beta}-OH Steroid Dehydrogenase Isoforms in Aortic Endothelial Cells Hypertension, January 1, 1998; 31(1): 459 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Smith, L. A. Salamonsen, P. A. Komesaroff, K. X. Z. Li, K. M. Myles, M. Lawrence, and Z. Krozowski 11{beta}-Hydroxysteroid Dehydrogenase Type II in the Human Endometrium: Localization and Activity during the Menstrual Cycle J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4252 - 4257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. X. Z. Li, V. R. Obeyesekere, Z. S. Krozowski, and P. Ferrari Oxoreductase and Dehydrogenase Activities of the Human and Rat 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Enzyme Endocrinology, July 1, 1997; 138(7): 2948 - 2952. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
