The low energy X-ray response of the LiF:Mg:Cu:P thermoluminescent dosemeter: a comparison with LiF:Mg:Ti.

LiF:Mg:Cu:P thermoluminescent dosemeters (TLD) can be used for the same X-ray dosimetry applications as LiF:Mg:Ti, with each type having the disadvantage of a response dependent on energy, particularly at low energies. Measurements were made of the response per unit air kerma of LiF:Mg:Cu:P and LiF:Mg:Ti to nine quasi-monoenergetic X-ray beams with mean energies from 12 keV to 208 keV. Each measurement was normalized to the value produced by 6 MV X-rays. LiF:Mg:Cu:P was found to under-respond to a majority of these radiations whereas LiF:Mg:Ti over-responded to a majority. Their smallest relative measured response was produced by the lowest energy beam, and the maximum measured relative response of 1.15+/-0.07 and 1.21+/-0.07 for LiF:Mg:Cu:P and LiF:Mg:Ti, respectively, occurred at 33 keV. Energy response coefficients were derived from these measurements to estimate the error introduced by using either type of TLD to measure the dose from an X-ray spectrum different to that used for its absolute response calibration. It was calculated that if the response of either type of TLD was calibrated at 100 kVp, then an error of no more than +/-2% would be introduced into measurements of tube output at potentials of 50-130 kVp. LiF:Mg:Cu:P was found to introduce a larger error (up to 30%) into the measurement of body exit dose than LiF:Mg:Ti at tube potentials of 40-150 kVp, if its absolute response was calibrated using the corresponding body entrance beam. The method should allow this type of error to be estimated in other dosimetry applications for either type of TLD.

Correlation of clinical, endocrine and molecular abnormalities with in vivo responses to high-dose testosterone in patients with partial androgen insensitivity syndrome.

OBJECTIVE: To investigate the responses of two patients previously diagnosed as Reifenstein's syndrome to graded high-dose testosterone in terms of hormone levels, nitrogen balance and sebum secretion and to attempt to correlate these parameters with the properties of their androgen receptors and mutations in the androgen receptor gene. DESIGN: Nitrogen balance was determined by comparing controlled nitrogen intake to the amount excreted. Sebum excretion was measured on the forehead. Patients were studied during control periods (no treatment) and during administration of testosterone propionate. Blood samples were used as a source of genomic DNA and to measure peripheral hormone levels; androgen receptor binding was determined using genital skin fibroblasts. PATIENTS: Two patients of XY karyotype, with ambiguous external genitalia and problems of testicular descent who had required mastectomy as teenagers. Normal male controls of proven fertility. MEASUREMENTS: Nitrogen balance, sebum excretion rate and peripheral hormone levels (testosterone, dihydrotestosterone, LH and FSH) were studied before and after testosterone therapy (1 or 5 mg/kg/day). Genomic DNA was extracted from peripheral blood leucocytes and regions of the androgen receptor gene amplified by polymerase chain reaction using pairs of specific primers. Mobility of amplified DNA from patients was analysed on denaturing gradient acrylamide gels and fragments differing in mobility from those of normal controls were sequenced. Fibroblasts were cultured from scrotal skin biopsies and androgen receptor binding parameters, subcellular localization and up-regulation were determined. RESULTS: Testosterone therapy resulted in raised plasma testosterone, dihydrotestosterone and oestradiol in both patients. In patient 1 (lesser genital abnormality), LH was suppressed by 5 mg/kg/day testosterone to the upper limit of the normal range but FSH remained low normal. Both LH and FSH were suppressed by testosterone treatment in patient 2 (greater genital abnormality). Nitrogen retention was increased in both patients (4.2 and 3.0 g/24 h respectively); sebum excretion rate increased to normal in patient 1 but showed no change in patient 2. Mutations in the androgen receptor gene were identified in both patients. In patient 1 a single nucleotide change from adenosine to guanosine resulted in the substitution of glycine for glutamic acid at position 772 within the hormone binding domain of the receptor. In patient 2 a single nucleotide mutation from guanosine to adenosine resulted in the substitution of lysine for arginine at position 608 (exon 3) situated in the second zinc finger of the DNA binding domain. Both patients had a normal number of androgen binding sites in genital skin fibroblasts but those in patient 1 showed reduced binding affinity and rapid dissociation of receptor/ligand complexes while those in patient 2 showed defective nuclear localization. CONCLUSION: In patients with partial androgen insensitivity syndrome the type of androgen receptor mutation and responses to short-term androgen treatment can be correlated with the individual's potential to virilize. If there is a mutation in the androgen receptor DNA binding domain the patient may show little ability to virilize either spontaneously at puberty or after androgen treatment. Sebum excretion appears to be more discriminating than nitrogen balance or gonadotrophin suppression as an index of tissue response to androgens.

Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2.

By inactivating potent glucocorticoid hormones (cortisol and corticosterone), 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) plays an important role in the placenta by controlling fetal exposure to maternal glucocorticoids, and in aldosterone target tissues by controlling ligand access to co-localized glucocorticoid and mineralocorticoid receptors. Amino acid sequence from homogeneous human placental 11 beta-HSD2 was used to isolate a 1897 bp cDNA encoding this enzyme (predicted M(r) 44126; predicted pI 9.9). Transfection into mammalian (CHO) cells produces 11 beta-HSD2 activity which is NAD(+)-dependent, is without reductase activity, avidly metabolizes glucocorticoids (Km values for corticosterone, cortisol and dexamethasone of 12.4 +/- 1.5, 43.9 +/- 8.5 and 119 +/- 15 nM respectively) and is inhibited by glycyrrhetinic acid and carbenoxolone (IC50 values 10-20 nM). Rabbit antisera recognizing 11 beta-HSD2 have been raised to an 11 beta-HSD2-(370--383)-peptide-carrier conjugate. Recombinant 11 beta-HSD2, like native human placental 11 beta-HSD2, is detectable with affinity labelling and anti-11 beta-HSD2 antisera, and appears to require little post-translational processing for activity. 11 beta-HSD2 mRNA (approximately 1.9 kb transcript) is expressed in placenta, aldosterone target tissues (kidney, parotid, colon and skin) and pancreas. In situ hybridization and immunohistochemistry localize abundant 11 beta-HSD2 expression to the distal nephron in human adult kidney and to the trophoblast in the placenta. 11 beta-HSD2 transcripts are expressed in fetal kidney (but not lung, liver or brain) at 21-26 weeks, suggesting that an 11 beta-HSD2 distribution resembling that in the adult is established by this stage in human development.

11 beta-Hydroxysteroid dehydrogenases: tissue-specific dictators of glucocorticoid action.

11 beta-HSD catalyses the interconversion of active and inactive corticosteroids and exists as two isoforms with less than 30% amino acid homology. The bi-directional NADP-dependent type 1 enzyme appears to function as a tissue-specific glucocorticoid provider. The uni-directional NAD-dependent type 2 enzyme functions as a tissue-specific glucocorticoid protector. The syndrome of AME is caused by mutations in the gene of 11 beta-HSD2. Placental 11 beta-HSD2 is a barrier to growth-retarding maternal glucocorticoids and may play a key role in prenatal programming of hypertension.

Alcohol inhibits 11-beta-hydroxysteroid dehydrogenase activity in rat kidney and liver.

Male Wistar rats were treated with different ethanol concentrations diluted in drinking water in order to evaluate the effect of acute ethanol intoxication on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity in liver and kidney tissue homogenates. Rats with the highest ethanol consumption (15% ethanol supplementation) showed a significant decrease in both hepatic and renal 11 beta-OHSD activity as compared to the control group (p < 0.005). In the same group, aldosterone plasma levels were significantly lower than in controls (p < 0.01), while corticosterone (B) plasma levels were slightly higher, suggesting that the increase in intrarenal B concentrations, probably related to the acute ethanol consumption, might be responsible for a nonspecific B mineralocorticoid activity.

'Liver-type' 11 beta-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the metabolism of corticosterone to inert 11-dehydrocorticosterone, thus preventing glucocorticoid access to otherwise non-selective renal mineralocorticoid receptors (MRs), producing aldosterone selectivity in vivo. At least two isoforms of 11 beta-HSD exist. One isoform (11 beta-HSD1) has been purified from rat liver and an encoding cDNA cloned from a rat liver library. Transfection of rat 11 beta-HSD1 cDNA into amphibian cells with a mineralocorticoid phenotype encodes 11 beta-reductase activity (activation of inert 11-dehydrocorticosterone) suggesting that 11 beta-HSD1 does not have the necessary properties to protect renal MRs from exposure to glucocorticoids. This function is likely to reside in a second 11 beta-HSD isoform. 11 beta-HSD1 is co-localized with glucocorticoid receptors (GRs) and may modulate glucocorticoid access to this receptor type. To examine the predominant direction of 11 beta-HSD1 activity in intact mammalian cells, and the possible role of 11 beta-HSD in regulating glucocorticoid access to GRs, we transfected rat 11 beta-HSD1 cDNA into a mammalian kidney-derived cell system (COS-7) which has little endogenous 11 beta-HSD activity or mRNA expression. Homogenates of COS-7 cells transfected with increasing amounts of 11 beta-HSD cDNA exhibited a dose-related increase in 11 beta-dehydrogenase activity. In contrast, intact cells did not convert corticosterone to 11-dehydrocorticosterone over 24 h, but showed a clear dose-related 11 beta-reductase activity, apparent within 4 h of addition of 11-dehydrocorticosterone to the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of 11 beta-hydroxysteroid dehydrogenase activity by the hypothalamic-pituitary-adrenal axis in the rat.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) inactivates glucocorticoids and thereby modulates their access to both mineralocorticoid and glucocorticoid receptors. Since 11 beta-OHSD activity influences the biological responses of the hypothalamic-pituitary-adrenal axis, it might be regulated by components of this axis. We examined 11 beta-OHSD activity in adrenalectomized rats treated for 9 days with dexamethasone and with or without ACTH. Adrenalectomy and low-dose (2 micrograms/day) dexamethasone had no effect on 11 beta-OHSD activity in renal cortex, hippocampus or heart, and reduced enzyme activity in aorta. High-dose dexamethasone (50 micrograms/day) had no effect in renal cortex but increased enzyme activity by at least 50% in all other sites. This effect of dexamethasone was unaffected by the co-administration of ACTH. We also examined the metabolism of dexamethasone by 11 beta-OHSD in homogenized rat tissues. Only in kidney, in the presence of NAD rather than NADP, was dexamethasone converted to a more polar metabolite previously identified as 11-dehydrodexamethasone. We conclude that: dexamethasone induction of 11 beta-OHSD is tissue-specific, and includes vascular tissues and hippocampus but not kidney; this tissue-specificity may be explained by contrasting metabolism of dexamethasone by the isoforms of 11 beta-OHSD; fluctuations of glucocorticoid levels within the physiological range may not have a biologically significant effect on 11 beta-OHSD activity; and the inhibitory effect of ACTH, observed previously in humans, is likely to depend on the presence of intact adrenal glands.

Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess.

Excessive ingestion of licorice induces a syndrome of hypokalemia and hypertension that reflects increased activation of renal mineralocorticoid receptors by cortisol. A similar syndrome of cortisol-dependent mineralocorticoid excess occurs in congenital deficiency of the enzyme 11 beta-hydroxysteroid dehydrogenase, which normally inactivates cortisol to cortisone. It has been shown that licorice inhibits 11 beta-dehydrogenase, preventing local inactivation of cortisol and allowing cortisol inappropriate access to intrinsically nonspecific renal mineralocorticoid receptors. Further studies with licorice and its derivatives have revealed a widespread role for 11 beta-dehydrogenase in regulating tissue sensitivity to cortisol. Deficient 11 beta-dehydrogenase activity provides a novel pathogenetic mechanism for hypertension, and current research suggests that several common forms of hypertension can be explained by the mechanisms that operate in licorice-induced hypertension.

Apparent mineralocorticoid excess.

In 1979, Ulick and New first coined the term Apparent Mineralocorticoid Excess (AME) for a syndrome of hypertension, hypokalaemia, suppressed renin-angiotensin-aldosterone axis and raised urinary ratio of 11 beta-hydroxy to 11-oxo metabolities of cortisol (suggesting a failure of conversion of cortisol to cortisone). In retrospect, the first case was described in 1974 and since then over 20 children have been reported worldwide but only one adult patient. The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) confers aldosterone specificity on intrinsically nonspecific kidney mineralocorticoid receptors by converting the active glucocorticoid cortisol to its inactive 11-oxo form (cortisone). Patients with AME have a deficiency of this enzyme which allows physiological levels of cortisol to flood mineralocorticoid receptors. Dexamethasone, by suppressing adrenal cortisol production, reverts the biochemistry but not usually the BP to normal. Liquorice inhibits 11beta-OHSD by virtue of its active ingredient glycyrrhetinic acid, resulting in an identical clinical picture. Renal 11beta-OHSD is the protagonist in AME but this enzyme is found in many other tissues including liver, placenta and vasculature, and one-third of essential hypertensives have deficient 11beta-OHSD. The placental isoform is thought to be the main barrier to maternal glucocorticoids reaching the fetus. The lowest rat placental 11beta-OHSD activity is found in the largest placentas corresponding to the smallest fetuses (presumably exposed to the highest glucocorticoid levels). This is the group which in humans are most at risk of developing hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Rat liver 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid encodes oxoreductase activity in a mineralocorticoid-responsive toad bladder cell line.

The mineralocorticoid receptor displays equal affinity for aldosterone and corticosterone. It has been proposed that aldosterone selectivity in vivo is achieved by the conversion of corticosterone into its inactive metabolite 11-dehydrocorticosterone by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). To test this hypothesis, we transfected rat liver 11 beta HSD cDNA into TBM cells, a sodium-transporting cell line. These cells respond equally well to aldosterone and corticosterone, indicating that endogenous 11 beta HSD is expressed at low levels in TBM cells. Although exogenous rat liver 11 beta HSD was expressed at high levels in transfected cells, mineralocorticoid selectivity was not observed. By contrast, the biologically inactive 11-dehydrocorticosterone was readily converted into corticosterone, a potent agonist for sodium transport. Our results indicate that rat liver 11 beta HSD behaves predominantly as a reductase in TBM cells. Another 11 beta HSD isoform is likely to be responsible for the dehydrogenase reaction in aldosterone-responsive cells.

Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man.

1. 11 beta-Hydroxysteroid dehydrogenase converts cortisol to inactive cortisone in man. In distal renal tubules, this inactivation protects mineralocorticoid receptors from cortisol. Congenital 11 beta-hydroxysteroid dehydrogenase deficiency and inhibition of 11 beta-hydroxysteroid dehydrogenase by liquorice or carbenoxolone result in cortisol-dependent hypokalaemia and hypertension. 2. 11 beta-Hydroxysteroid dehydrogenase is expressed in vascular smooth muscle. Both glucocorticoids and mineralocorticoids potentiate vascular responses to noradrenaline. 11 beta-Hydroxysteroid dehydrogenase activity may therefore influence vascular tone. 3. Experiments were performed in healthy subjects with and without 7 days of oral administration of 11 beta-hydroxysteroid dehydrogenase inhibitors (liquorice or carbenoxolone), and in a patient with congenital 11 beta-hydroxysteroid dehydrogenase deficiency. We measured the following parameters: dermal vasoconstriction after topical application of cortisol, forearm blood flow during brachial artery infusion of cortisol or noradrenaline, and blood pressure during systemic infusion of noradrenaline. 4. Cortisol-induced dermal vasoconstriction was increased by liquorice (23 +/- 6 to 52 +/- 7 units; P < 0.04) and in congenital 11 beta-hydroxysteroid dehydrogenase deficiency (87 units). In congenital 11 beta-hydroxysteroid dehydrogenase deficiency intraarterial infusion of cortisol caused vasoconstriction (20% reduction in blood flow in the infused arm) and accentuated the response to application of lower-body negative pressure, which stimulates sympathetically mediated vasoconstriction (35% reduction). However, intra-arterial infusion of cortisol had no effect in healthy subjects either with or without administration of liquorice. 5. Carbenoxolone potentiated both noradrenaline induced forearm vasoconstriction (P < 0.01) and pressor response (P < 0.001). 6. We conclude that 11 beta-hydroxysteroid dehydrogenase modulates the access of cortisol to vascular receptors and thereby influences vascular sensitivity to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle and heart: implications for cardiovascular responses to glucocorticoids.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in the rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. We have previously demonstrated that cortisol-induced cutaneous vasoconstriction in man is potentiated by the 11 beta-OHSD inhibitor glycyrrhetinic acid, suggesting that 11 beta-OHSD may protect vascular corticosteroid receptors. In this study we report quantitation of 11 beta-OHSD bioactivity in homogenates of rat aorta, mesenteric artery, caudal artery, and heart, expressed as the percent in vitro conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone. Nicotinamide adenine dinucleotide phosphate (NADP+)-dependent 11 beta-OHSD activity was found in all of these tissues and was significantly higher in resistance vessels than aorta (P less than 0.05) [without NADP+: caudal artery (4.2 +/- 0.2%) greater than mesenteric artery (2.5 +/- 0.7%) = heart (1.67 +/- 0.2%) greater than aorta (0.79 +/- 0.2%); with 200 microM NADP+: caudal artery (43.9 +/- 2.1%) greater than heart (20.6 +/- 1.0%) = mesenteric artery (17.7 +/- 3.1%) = aorta (11.4 +/- 0.4%); heart greater than aorta]. All of these were lower than renal cortex (29.4 +/- 1.8% without NADP+; 82.4 +/- 0.4% with NADP+; P less than 0.001). 3H-11-dehydrocorticosterone was the major metabolite of 3H-corticosterone (greater than 97% of 3H-corticosterone metabolized). Reduction of 3H-11-dehydrocorticosterone to 3H-corticosterone was not detected in these experiments. We also report localization of 11 beta-OHSD-like immunoreactivity by immunohistochemistry using antisera raised against rat liver 11 beta-OHSD, and of 11 beta-OHSD messenger RNA expression by in situ hybridization using complementary RNA probes transcribed from complementary DNA encoding rat liver 11 beta-OHSD. We found 11 beta-OHSD immunoreactivity and messenger RNA expression in vascular and cardiac smooth muscle cytoplasm but not in endothelium. Thus, 11 beta-OHSD is appropriately sited to modulate access of corticosterone to vascular receptors and could influence vascular resistance, cardiac output and thereby blood pressure.

The cortisol-cortisone shuttle and hypertension.

11 beta-OHSD is an enzyme complex consisting of 11 beta-DH, converting cortisol to cortisone in man and an 11-keto-reductase performing the reverse reaction. Congenital deficiency of 11 beta-DH should be considered in any child presenting with mineralocorticoid hypertension and suppression of the renin-angiotensin-aldosterone axis. The keystone to diagnosis is the demonstration of a reduced daily production rate of cortisol and an increase in its plasma half-life. In the majority of cases diagnosis can be made from a urinary steroid metabolite profile indicating a high excretion of cortisol relative to cortisone metabolites. Cortisol is the responsible mineralocorticoid, and as such treatment with the pure glucocorticoid dexamethasone will prevent life-threatening hypokalemia, although additional anti-hypertensive drugs are usually required to control blood pressure. Liquorice and carbenoxolone, for years thought to be direct "agonists" of the mineralocorticoid receptor, in fact cause sodium retention through inhibition of 11 beta-DH. The demonstration of 11 beta-DH activity in the vasculature raises the possibility that it locally modules access of glucocorticoids to mineralocorticoid and possibly glucocorticoid receptors in the vessel wall. It remains possible that subtle alterations of this cortisol-cortisone shuttle are responsible for other forms of hypertension which are currently classified under the umbrella diagnosis of essential hypertension.

11 beta-hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus, and cortex.

In peripheral aldosterone target sites (e.g., kidney), 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) metabolizes corticosterone to inactive 11-dehydrocorticosterone and thus protects mineralocorticoid receptors from exposure to corticosterone in vivo. We have investigated whether 11 beta-OHSD could account for the site-specific differences in corticosteroid receptor sensitivity to corticosterone in rat brain. Enzyme activity, estimated as the percentage conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in the presence of NADP+ (200 microM), was: hippocampus, 55.8 +/- 2.7%; cortex, 52 +/- 3.1%; pituitary; 40 +/- 2%, hypothalamus, 26.1 +/- 1.2%; brain stem, 21.4 +/- 1.7%; and spinal cord, 12.3 +/- 1.8%. Northern blots, using [32P]dCTP-labeled probes from an 11 beta-OHSD cDNA clone derived from rat liver, showed expression of a single mRNA species in all brain areas, of identical size to 11 beta-OHSD mRNA in liver and kidney. Highest expression was found in hippocampus and cortex. In situ hybridization, using [35S]UTP-labeled cRNA probes, localized high mRNA expression to cerebral cortex (particularly parietal cortex, layer IV), hippocampus (highest in CA3), hypothalamic medial preoptic area and arcuate nuclei and anterior pituitary. In conclusion, there is localized 11 beta-OHSD mRNA expression and enzyme bioactivity in rat brain. The distribution of 11 beta-OHSD corresponds to areas of reduced glucocorticoid or mineralocorticoid receptor affinity for corticosterone. Therefore, 11 beta-OHSD may regulate the access of corticosterone to cerebral mineralocorticoid and/or glucocorticoid receptors and thus modulate corticosteroid effects on brain function.

Renal 11-beta-hydroxysteroid dehydrogenase: a mechanism ensuring mineralocorticoid specificity.

In vitro studies with mineralocorticoid receptors (MR) have shown that they are non-specific and do not distinguish between glucocorticoids (cortisol in man, corticosterone in rodents) and aldosterone. These findings contrast with in vivo aldosterone selectivity. Our studies on the congenital deficiency of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD; which converts cortisol to cortisone or corticosterone to 11-dehydrocorticosterone) and acquired deficiency secondary to liquorice or carbenoxolone indicate that this enzyme plays a crucial role in protecting the MR from glucocorticoid exposure. The localisation of 11 beta-OHSD in both the proximal and distal nephron suggests that it has both an autocrine and a paracrine role. The presence of this protective mechanism in the toad bladder suggests that it is at least 300 million years old.

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11 beta-hydroxysteroid dehydrogenase activity in man.

1. 11-beta-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11 beta-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11 beta-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex. 2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11 beta-dehydrogenase (as measured by a rise in the plasma half-life of [11 alpha-3H]cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate). 3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11 beta-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.