Hexose-6-Phosphate Dehydrogenase and 11β-Hydroxysteroid Dehydrogenase-1 Tissue Distribution in the Rat
- 26 November 2007
- journal article
- Published by The Endocrine Society in Endocrinology
- Vol. 149 (2), 525-533
- https://doi.org/10.1210/en.2007-0328
Abstract
Intracellular concentrations of the glucocorticoids cortisol and corticosterone are modulated by the enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD) 1 and 2. 11β-HSD1 is a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent microsomal reductase that converts the inactive glucocorticoids cortisone and 11-dehydrocorticosterone to their active forms, cortisol and corticosterone. Hexose-6-phosphate dehydrogenase (H6PDH) is an enzyme that generates NADPH from oxidized NADP (NADP+) within the endoplasmic reticulum. In the absence of NADPH or H6PDH to regenerate NADPH, 11β-HSD1 acts as a dehydrogenase and inactivates glucocorticoids, as does 11β-HSD2. A monoclonal antibody against H6PDH was produced to study the possibility that 11β-HSD1 in the absence of H6PDH may be responsible for hydroxysteroid dehydrogenase activity in tissues that do not express significant amounts of 11β-HSD2. H6PDH and 11β-HSD1 expression was surveyed in a variety of rat tissues by real-time RT-PCR, Western blot analysis, and immunohistochemistry. H6PDH was found in a wide variety of tissues, with the greatest concentrations in the liver, kidney, and Leydig cells. Although the brain as a whole did not express significant amounts of H6PDH, some neurons were clearly immunoreactive by immunohistochemistry. H6PDH was amply expressed in most tissues examined in which 11β-HSD1 was also expressed, with the notable exception of the renal interstitial cells, in which dehydrogenase activity by 11β-HSD1 probably moderates activation of the glucocorticoid receptor because rat renal interstitial cells do not have significant amounts of mineralocorticoid receptors. This antibody against the H6PDH should prove useful for further studies of enzyme activity requiring NADPH generation within the endoplasmic reticulum.Keywords
This publication has 74 references indexed in Scilit:
- Hexose-6-phosphate Dehydrogenase Modulates 11β-Hydroxysteroid Dehydrogenase Type 1-Dependent Metabolism of 7-keto- and 7β-hydroxy-neurosteroidsPLOS ONE, 2007
- Mineralocorticoid Receptors and Cardiovascular DamageHypertension, 2006
- Is aldosterone synthesized within the rat brain?American Journal of Physiology-Endocrinology and Metabolism, 2005
- Hexose‐6‐phosphate dehydrogenase determines the reaction direction of 11β‐hydroxysteroid dehydrogenase type 1 as an oxoreductaseFEBS Letters, 2004
- Excess ldosterone Is Associated With Alterations of Myocardial Texture in Primary AldosteronismHypertension, 2002
- Cloning and tissue distribution of the human 1 lβ-hydroxysteroid dehydrogenase type 2 enzymeMolecular and Cellular Endocrinology, 1994
- Biologic Differences Between Vasodilator Prostaglandins and Medullipin IThe American Journal of the Medical Sciences, 1992
- Evidence for kinetically distinct forms of corticosteroid 11β-dehydrogenase in rat liver microsomesJournal of Steroid Biochemistry, 1989
- Phenobarbital-induced increase of the hexose 6-phosphate dehydrogenase activityBiochemical and Biophysical Research Communications, 1974
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970