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-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol
1Endocrine Section and Research Service, G. V. (Sonny) Montgomery Veterans Affairs Medical Center, 2Division of Endocrinology, and 3Department of Pathology, The University of Mississippi Medical Center, Jackson, Mississippi 39216; and Departments of 4Medicine and 5Veterinary Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri 65211
Submitted 16 September 2002 ; accepted in final form 6 April 2003
The 11
-hydroxysteroid dehydrogenase (11
HSD) type 1
(11
HSD1) enzyme is an NADP+-dependent oxidoreductase, usually
reductase, of major glucocorticoids. The NAD+-dependent type 2
(11
HSD2) enzyme is an oxidase that inactivates cortisol and
corticosterone, conferring extrinsic specificity of the mineralocorticoid
receptor for aldosterone. We reported that addition of a reducing agent to
renal homogenates results in the monomerization of 11
HSD2 dimers and a
significant increase in NAD+-dependent corticosterone conversion.
Estrogenic effects on expression, dimerization, and activity of the kidney
11
HSD1 and -2 enzymes are described herein. Renal 11
HSD1 mRNA and
protein expressions were decreased to very low levels by estradiol
(E2) treatment of both intact and castrated male rats; testosterone
had no effect. NADP+-dependent enzymatic activity of renal
homogenates from E2-treated rats measured under nonreducing
conditions was less than that of homogenates from intact animals. Addition of
10 mM DTT to aliquots from these same homogenates abrogated the difference in
NADP+-dependent activity between E2-treated and control
rats. In contrast, 11
HSD2 mRNA and protein expressions were
significantly increased by E2 treatment. There was a marked
increase in the number of juxtamedullary proximal tubules stained by the
antibody against 11
HSD2 after the administration of E2.
Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone
excreted in the urine nor their ratio differed between E2- and
vehicle-treated rats. NAD+-dependent enzymatic activity in the
absence or presence of a reducing agent demonstrated that the increase in
11
HSD2 protein was not associated with an increase in in vitro activity
unless the dimers were reduced to monomers.
hypertension; aldosterone
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