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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) by licorice-derived compounds and in cases of idiopathic impairment of this enzyme is known to result in hypermineralocorticoid syndromes, reflecting corticosteroid receptor activation by excess intracellular glucocorticoids. In this paper we address the question of whether or not endogenous inhibitors of 11 beta-OHSD exist that might cause pathological glucocorticoid metabolism. Using microsomal preparations we have demonstrated that bile acids are potent inhibitors of rat renal and human hepatic 11 beta-OHSD, with lithocholic acid exerting the strongest effect. The human renal enzyme is affected to a lesser extent. Serum of patients with cholestatic liver cirrhosis also inhibited 11 beta-OHSD activity, in parallel with total bile acid concentration. Cholesterol and its precursor lanosterol inhibited the enzymatic activity in microsomes from rat and human kidney cortex and human liver. We conclude that bile acids could contribute to the abnormalities of cortisol metabolism observed in cholestatic liver cirrhosis.
Steroids 1994 Feb
PMID:Endogenous inhibitors of 11 beta-OHSD: existence and possible significance. 819 42

Licorice has long been known to promote the healing of ulcers. In the 1950s, studies with licorice-derived compounds revealed that the anti-ulcer effects of licorice are due to inhibition of 15-hydroxyprostaglandin dehydrogenase and delta 13-prostaglandin reductase. 15-Hydroxyprostaglandin dehydrogenase converts prostaglandins E2 and F2 alpha to 15-ketoprostaglandins, which are inactive. delta 13-Prostaglandin reductase metabolizes the inactive delta 13-prostaglandin to 13,14-dihydro,15-ketoprostaglandin, which is further metabolized and excreted in urine. Thus, licorice-derived compounds have the effect of raising the local concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach, leading to healing of ulcers. 11 beta-Hydroxysteroid dehydrogenase, which also is inhibited by licorice-derived compounds, shares a common ancestor with 15-hydroxyprostaglandin dehydrogenase. Both enzymes are homologous to Streptomyces hydrogenans 3 alpha,20 beta-hydroxysteroid dehydrogenase, which also is inhibited by licorice. Thus, licorice inhibits enzymes that diverged at least 2 billion years ago from a common ancestor. Other oxidoreductases in bacteria, plants, and animals that are inhibited by licorice-derived compounds are likely to be discovered in the future.
Steroids 1994 Feb
PMID:Licorice and enzymes other than 11 beta-hydroxysteroid dehydrogenase: an evolutionary perspective. 819 43

Mineralocorticoid receptors (MR) are protected from the effects of endogenous glucocorticoids (GC) in mineralocorticoid (MC) target tissues such as the kidney and the parotid gland. This protection is thought to be provided by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD metabolizes cortisol (in humans) and corticosterone (B) (in the rat) to cortisone and 11-dehydro-B, their respective inactive dehydro products. We have previously shown that the antinatriuretic actions of the MC deoxycorticosterone (DOC) are amplified in carbenoxolone (CBX) treated adrenalectomized (ADX) rats. CBX is believed to inhibit 11 beta-OHSD activity; DOC, however, is not a substrate for this enzyme. We now report on 11-desoxycortisol (11-desoxy-F) and 2 alpha-methylcortisone, substances which possess no intrinsic antinatriuretic activity, are not metabolized by 11 beta-OHSD and yet cause Na+ retention in CBX-treated ADX rats. Given that none of the above steroids are substrates for 11 beta-OHSD it is unlikely that the inhibition of this enzyme is involved in the unmasking of the Na+ retention observed when these substances are given to CBX-treated animals. These results provide further evidence for an additional protective mechanism, that protects MR from the inappropriate binding of excessive amounts of endogenous MCs.
Steroids 1994 Feb
PMID:Other physiological considerations of protective mechanisms of mineralocorticoid action. 819 44

The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are closely related members of the nuclear receptor superfamily. Despite marked functional similarities and a high degree of sequence conservation between MR and GR, the mineralocorticoid and glucocorticoid hormones elicit markedly different physiological effects, even in cells expressing both receptors. Hormone specificity is, in part, determined by the actions of 11 beta-hydroxysteroid dehydrogenase. However, other mechanisms must obtain in cells that express both receptors and respond differentially to the two classes of hormone. Indeed, MR and GR, while functionally redundant in some contexts, in others display distinct transcriptional specificities. In particular, in the presence of members of the AP1 family of regulatory factors, cJun and cFos, a composite response element, plfG, is GR-specific. Transcription from a plfG-linked gene is stimulated by GR in the presence of cJun and repressed by GR in the presence of cJun and cFos. MR neither stimulates nor represses transcription in the same contexts, thus indicating that receptor transcriptional specificities can be distinguished by differential interactions with nonreceptor factors at a composite response element. The implications of these findings for mineralocorticoid and glucocorticoid hormone specificity in various tissues are discussed.
Steroids 1994 Feb
PMID:A mechanistic basis for distinct mineralocorticoid and glucocorticoid receptor transcriptional specificities. 819 46

It has been shown that stress or disease-induced increases in plasma corticosterone result in diminished testosterone secretion from the testes. This article reviews investigations from our laboratories that explore the role of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in this process. It is proposed that the level of 11 beta-OHSD in Leydig cells dictates the level of intracellular glucocorticoid available to the glucocorticoid receptor and thus the potency of corticosteroid as an inhibitor of testosterone secretion. Stressed and unstressed rats were housed under simulated natural conditions in a Visible Burrow System. Stressed animals showed elevated plasma corticosteroid, lowered plasma testosterone, and diminished testicular 11 beta-OHSD, Immunocytochemical analysis showed that only Leydig cells of the rat testis contain 11 beta-OHSD and glucocorticoid receptors. Half-maximal inhibition of testosterone by Leydig cells required 1.5 nM dexamethasone or 0.4 microM corticosterone. Glycyrrhetinic acid, an inhibitor of 11 beta-OHSD, increased the potency of corticosterone, but did not affect dexamethasone based inhibition. The glucocorticoid receptor blocker, RU 486, prevented inhibition by both corticosterone and dexamethasone. Other classes of steroid were not inhibitors of testosterone biosynthesis. Thus, 11 beta-OHSD oxidizes corticosterone to the inactive metabolite 11-dehydrocorticosterone, relieving steroid-dependent inhibition of Leydig cell function. Lowered enzyme activity increases glucocorticoid dependent inhibition of testosterone production. We conclude that the evidence supports a role of 11 beta-OHSD in testosterone secretion by the testes.
Steroids 1994 Feb
PMID:Comparative aspects of 11 beta-hydroxysteroid dehydrogenase. Testicular 11 beta-hydroxysteroid dehydrogenase: development of a model for the mediation of Leydig cell function by corticosteroids. 819 50

The syndrome of apparent mineralocorticoid excess (AME) is currently understood to reflect impaired peripheral metabolism of cortisol, which is then able to activate the non-selective mineralocorticoid (MC) receptor. The failure of glucocorticoid inactivation at the MC target tissue level in AME involves abnormal activity of 11 beta-hydroxysteroid dehydrogenase, with impaired conversion of cortisol to cortisone, and also of 5 beta-reductase. We have discovered a new form of AME (Type II) in four patients with the same clinical picture of hypertension, hypokalemia, and suppressed renin-angiotensin-aldosterone system, but in whom this conversion seems either to be normal (since cortisol to cortisone metabolite ratio is normal) or to be impaired in both directions, leaving the ratio unchanged. Both types are characterized by a profound decrease in cortisol turnover quotient and Ring A reduction constant. Short-term dexamethasone treatment is effective in correcting the MC-derived abnormalities, while in the long term the addition of other antihypertensive drugs may be required to control the severity of hypertension.
Steroids 1994 Feb
PMID:Apparent mineralocorticoid excess type II. 819 52

Elucidation of a role for 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in modulating ligand access to renal mineralocorticoid receptors, together with identification of expression of the enzyme in most mammalian tissues, has raised the possibility (i) that glucocorticoid metabolism might influence corticosteroid receptor activation in other sites which are relevant to blood pressure control (e.g., vascular smooth muscle), and (ii) that abnormal 11 beta-OHSD expression might play a pathogenic role in common forms of hypertension (e.g., essential hypertension and the syndrome of ectopic ACTH secretion). This article reviews data from human experiments which suggest that 11 beta-OHSD has tissue-specific actions which can increase or decrease sensitivity of both mineralocorticoid and glucocorticoid receptors to cortisol, and that assessment of cortisol sensitivity may prove equally important as assessment of cortisol secretion rates in hypertensive patients.
Steroids 1994 Feb
PMID:Organ-specific actions of 11 beta-hydroxysteroid dehydrogenase in humans: implications for the pathophysiology of hypertension. 819 53

In normal physiology 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the mineralocorticoid receptor (MR) from glucocorticoid excess. In the rat, however, 11 beta-OHSD mRNA and activity is widespread, suggesting that it may also play a role in regulating ligand access to the glucocorticoid receptor (GR). We have studied the role of the 11 beta-OHSD in modulating corticosteroid hormone action in rat pituitary GH3 cells (glucocorticoids inhibit prolactin gene transcription) and renal epithelial NRK-52E cells (mineralocorticoids increase Na-K ATPase subunit gene expression) in culture. Both cell lines express high levels of 11 beta-OHSD activity, and Northern/Western blot analyses using a rat cDNA probe and antisera raised against rat liver 11 beta-OHSD reveal a single 1.4 Kb mRNA encoding an enzyme of molecular size 34 kDa. In GH3 cells, prolactin gene transcription was unaffected by corticosterone (B) in doses of 10(-8) to 10(-6) M. When 11 beta-OHSD activity was inhibited with the licorice derivative, glycyrrhetinic acid (GE); however, 10(-6) M B inhibited prolactin (PRL) mRNA levels to the same degree as an equimolar concentration of the GR agonist RU 28362. This effect was blocked by co-incubation with the GR antagonist RU 38486. In NRK-52E cells, co-incubation with B and GE resulted in a marked increase in alpha 1/beta 1 Na-K ATPase subunit mRNA levels when compared with GE and/or B alone and this effect could be blocked by administration of the MR antagonist RU 26752.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1994 Feb
PMID:11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action. 819 54

In vivo, corticosterone and 11-dehydrocorticosterone are interconverted in the liver and possibly kidney by 11 beta-hydroxysteroid dehydrogenase. In an effort to evaluate the relevance of this reversible reaction in relation to urinary sodium and potassium excretion, we investigated the effects of 11-dehydrocorticosterone in the presence and absence of carbenoxolone, a potent inhibitor of the oxidative component of 11 beta-hydroxysteroid dehydrogenase, and compared them with the effects of similar doses of corticosterone in carbenoxolone-treated rats. All experiments were performed on adrenalectomized male rats. Here we describe that in carbenoxolone-treated rats 11-dehydrocorticosterone and corticosterone display antinatriuretic activity, although under the conditions of this study 11-dehydrocorticosterone is a more potent sodium retainer than its parent steroid corticosterone. In addition, the antinatriuretic effects of 11-dehydrocorticosterone (like the antinatriuretic effects of corticosterone in carbenoxolone-treated rats) were blocked by the specific antimineralocorticoid RU28318.
Steroids 1993 Jan
PMID:11-Dehydrocorticosterone in the presence of carbenoxolone is a more potent sodium retainer than corticosterone. 843 Apr 42

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11-HSD) in the major organs of the rat by the inhibitor glycyrrhetinic acid (a component of licorice) was investigated. The inhibitor decreased 11-HSD levels in most organs after intraperitoneal injection. The effect was dose dependent, was maximally effective 3 hours after administration, and was completely reversed at 24 hours. The magnitude and patterns of effectiveness differed between tissues. It was concluded that the inhibition of 11-HSD by glycyrrhetinic acid is not restricted to one or a few organs, but is broadly based.
Steroids 1993 Apr
PMID:Inhibition by glycyrrhetinic acid of rat tissue 11 beta-hydroxysteroid dehydrogenase in vivo. 849 4


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