Hydroxysteroid dehydrogenase inhibition

Bail, J, Laroche,T, Marre-Foumier, F and Habrioux, G (1998) Aromatase and 17P-hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett., 133, 101-106. 

Carbenoxolone (B) is a derivative of glycyrrhetinic acid, which occurs in the sap of licorice root (succus Uquiri-tiae). Carbenoxolone stimulates mucus production. At the same time, it has a mineralocorticoid-like action (due to inhibition of 11-p-hydroxysteroid dehydrogenase) that promotes renal reabsorption of NaCl and water. It may, therefore, exacerbate hypertensioa congestive heart failure, or edemas. It is obsolete. 

Penning, T. M., Sharp, R. B., and Krieger, N. R. (1985). Purification and properties of 3 alpha-hydroxysteroid dehydrogenase from rat brain cytosol. Inhibition by nonsteroidal anti-inflammatory drugs and progestins. J. Biol. Chem. 260, 15266—15272. 

A series of dibenzazocines was designed for application in the synthesis of homochiral polyamide polymers <1998TA3497>. Bis-oxo-tetrahydrodibenzazocines showed picomolar to nanomolar inhibition of 17/ -hydroxysteroid dehydrogenase of type 3 <2006BML1532>. Colchicine derivatives that contain the dibenzazocine moiety have been studied for their biological properties <2000BMC557>. 

Black cohosh 2. Geum chiloense 3. Liquorice 1. Cisplatin 2. Azathioprine 3. Cidosporin 4. Prednisolone t cytotoxic properties. Geum t plasma cidosporin levels 6-8-fold Unknown mechanism (black cohosh) Inhibits metabolizing enzymes. Glycyrrhizin present in liquorice inhibits the metabolizing enzyme of prednisolone, 11 beta-hydroxysteroid dehydrogenase, which converts the active metabolite to an inactive form. i clearance of prednisolone in healthy individuals Be aware. Advice is to avoid echinacea with immunosuppressants... 

Nordlie RC, Jorgenson RA. Latency and inhibitability by metabolites of glucose-6-phosphatase of permeable hepatocytes from fasted and fed rats. J. Biol. Chem. 1981 256 4768-4771. McCornuck KL, Wang X, Mick GJ. Evidence that the 11 P-hydroxysteroid dehydrogenase is regulated by pentose pathway flux. Studies in rat adipocytes and microsomes. J. Biol. Chem. 2006 281 341-347. 

The selectivity of hydrocortisone for the glucocorticoid receptor is not due to a different binding affinity of hydrocortisone to the two receptors but to the protection of the mineralocorticoid receptor by locally high concentrations of the enzyme 11 J-hydroxysteroid dehydrogenase, which converts cortisol (hydrocortisone) to the inactive cortisone. This enzyme is inhibited by one of the components of liquorice, and can occasionally harbour a genetic defect. Therefore both acquired (in liquorice addicts) and inherited syndromes of pseudohyperaldo-steronism can occasionally occur. 

Trilostane blocks the synthetic path earlier (3p-hydroxysteroid dehydrogenase) and thus also inhibits aldosterone synthesis. 

The active ingredients of licorice inhibit the breakdown of mineralocorticoids by inhibiting 11-beta-hydroxysteroid dehydrogenase type 2, and its adverse effects relate mainly to mineralocorticoid excess, with sodium retention, potassium loss, and inhibition of the renin-angiotensin-aldosterone system (36). 

Excessive licorice ingestion may cause a form of chloride resistant alkalosis. Black licorice contains glycyrrhizic acid, which inhibits the enzyme ll-p hydroxysteroid dehydrogenase, which in turn catalyzes the conversion of cortisol to cortisone. The excess cortisol exerts a mineralocorticoid effect on the distal tubule aldosterone receptors. ... 

Reidenberg, M. M. (2000). Environmental inhibition of llbeta-hydroxysteroid dehydrogenase. Toxicology 144,107-111. 

Norethynodrel, I7-a-ethinyl-17p-hj roxy-5(10)-estrene-3-one, increases eidrenal wei ts in intact female rats59. plasma and adrenal B levels decrease at the time of day dien values are normally highest. Clomiphene increases output of 17-oxysteroids in a patient with galactorrhea Cyano-trimethylandrostenolone, 2a-cyano-J4-, k, 17a-trimethyl-17p -OH- 5-androstene- 3-one, causes adrenal hypertrophy, a fall in adrenal venous 3 of male rats and inhibition of 3P-hydroxysteroid dehydrogenase l. Norethandrolone, 170(-ethyl-17P-0H- -norandrostene-3-one, stimulates the production of B by adrenals of castrated rats and increases pituitary ACTH content . This androgen partially reverses the E induced suppression of B production but not of the adrenal response to stresses. Testosterone, androstenedione, EHEA, estrone and estradiol has no effect on conversion of B to 18-OH B and Aldo by sheep adrenal mitochondria . 

Licorice has a well-documented mineralocorticoid-like effect. This effect occurs not because licorice mimics mineralocorticoid action, but rather is due to the inhibition of 11-P-hydroxysteroid dehydrogenase (1 lP-OHSD), the enzyme that catalyzes the conversion ofcortisol to cortisone (Stewart et al., 1987). Deficiency or inhibition of this enzyme leads to an increase in renal cortisol, which can bind to mineralocorticoid receptors (Stewart et al., 1987). The inhibiting substance in licorice appears to be 3-monoglucuronylglycyrrhetinic acid, a metabolite of glycyrrhetinic acid (Kato et al., 1995). This resultant mineralocorticoid effect may cause sodium retention, hypertension, hypokalemia, and suppression of plasma renin activity (Epstein et al. 977). 

The structure of cortisol differs from that of cortisone in that the C-ll hydroxyl group is replaced by a carbonyl group. Glycyrrhizic acid inhibits 1 l-/5-hydroxysteroid dehydrogenase, which prevents the deactivation of cortisol. Cortisone is administered to Addison s disease patients because it is converted to cortisol by 1 l-/5-hydroxysteroid dehydrogenase a reversible enzyme. 

LADHee and that the activity disappeared after carboxymethylation of a cysteine residue at the active site of LADH s [145]. In a recent study by Okuda and Okuda it was demonstrated that the -hydroxysteroid dehydrogenase activity in human liver was associated with a major isoenzyme of liver alcohol dehydrogenase (/82, 2) that the activity was inhibited by a chelating agent for Zn, which resides in the active site of the enzyme [146], Kinetic studies with the highly purified isoenzyme showed that neither a Theorell-Chance mechanism nor a simple ordered BiBi mechanism applied to the reaction. Evidence was obtained that the reaction was asymmetric in both directions. It has been established by Fukuba that the 4A-hydro-gen in NADH is involved [147]. 

Another anti-cancer mechanism of isoflavones may involve inhibition of key enzymes of estrogen metabolism, such as 3 p-hydroxy steroid dehydrogenase, 17P-hydroxysteroid dehydrogenase, 5a-reductase and aromatase, as a consequence of which the level of active steroid hormones is affected [81, 106, 107],... 

Lee, Y.S. Lorenzo, B.J. Koufis, T. Reidenberg, M.M. Grapefruit juice and its flavonoids inhibit lip-hydroxysteroid dehydrogenase. Clin.Pharmacol.Ther., 1996, 59, 62—71... 

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