Hydroxysteroid dehydrogenase

About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.

Regulation of 1lβ-Hydroxysteroid Dehydrogenase Activity in the Baboon Placenta by Estrogen*

Abstract: We have previously shown that the change in transuteroplacental cortisol (F)-cortisone (E) metabolism in vivo from preferential reduction (E to F) at midgestation to oxidation by term (F to E) does not occur in baboons in which the production or action of estrogen have been blocked. Moreover, because the administration of androstenedione (Δ4A) to baboons increased estradiol (E2) production at midgestation and induced a pattern of F-E metabolism similar to that at term, we suggested that estrogen regulates placental F-E interconversion. The present study was designed to ascertain whether estrogen regulates the activity of the placental 11β-hydroxysteroid dehydrogenase (11βHSD) enzyme catalyzing the oxidation of F to E. Placentas were obtained on day 100 (n = 10) and day 165 (n = 10) of gestation (term = day 184) from untreated baboons, on day 100 from animals (n = 7) treated with Δ4A between days 70-100 of gestation, and on day 165 from animals in which placental estrogen was decreased by fetectomy (n = 5)...

[69] Hydroxysteroid dehydrogenases: Hydroxysteroid + DPN + (TPN+) ⇄ Ketosteroid DPNH (TPNH) + H+

Abstract: Publisher Summary Stereospecific and reversible interconversions of hydroxyl and ketone functions of steroids are catalyzed by pyridine nucleotide-dependent hydroxysteroid dehydrogenases. Enzymes of this class are widely distributed among microorganisms and in animal tissues. Discrete catalytic proteins are concerned with reversible oxidations at specific locations, i.e., of 3 α -, 3 β -, ll β , 17 β -, 20 α -, and 20 β -hydroxysteroids. This chapter describes the assay method, purification procedure, and properties of hydroxysteroid dehydrogenases of Pseudomonas testosterone . 3 α -hydroxysteroid dehydrogenase ( α -enzyme) and (3 and 17) β -hydroxysteroid dehydrogenase ( β -enzyme) are two steroid-induced hydroxysteroid dehydrogenases that are isolated from Pseudomonas testosteroni , a soil microorganism which can utilize testosterone, or related steroid hormones, as the only source of organic carbon. Both α - and β -enzymes are inactivated by low concentrations of heavy metal ions and p -chloromercuribenzoate. Both enzymes are protected against inactivation by DPN. β -Enzyme is powerfully stabilized by low concentrations of estradiol-17 β . The asssay method, purification procedure, and properties of 20 β -hydroxysteroid dehydrogenase of Streptornyces hydrogenmas is described in the chapter.

Reduction of Zearalenone to Zearalenol in Female Rat Liver by 3α-Hydroxysteroid Dehydrogenase

Abstract: The distribution of the zearalenone reducing activity was investigated in liver fractions obtained by differential centrifugation of liver homogenate from adult female Sprague Dawley rats. The zearalenone reducing enzyme was identified as 3 alpha-hydroxysteroid dehydrogenase. At least two multiple forms occur of the enzyme with different subcellular locations and pH-optima. The activity was localized in the microsomes with NADH as coenzyme and in both microsomes and cytosol with NADPH.

Design, Synthesis, and Biological Evaluation of (Hydroxyphenyl)naphthalene and -quinoline Derivatives: Potent and Selective Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of Estrogen-Dependent Diseases

Abstract: Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the reduction of the weak estrogen estrone (E1) to the highly potent estradiol (E2). This reaction takes place in the target cell where the estrogenic effect is exerted via the estrogen receptor (ER). Estrogens, especially E2, are known to stimulate the proliferation of hormone-dependent diseases. 17β-HSD1 is overexpressed in many breast tumors. Thus, it is an attractive target for the treatment of these diseases. Ligand- and structure-based drug design led to the discovery of novel, selective, and potent inhibitors of 17β-HSD1. Phenyl-substituted bicyclic moieties were synthesized as mimics of the steroidal substrate. Computational methods were used to obtain insight into their interactions with the protein. Compound 5 turned out to be a highly potent inhibitor of 17β-HSD1 showing good selectivity (17β-HSD2, ERα and β), medium cell permeation, reasonable metabolic stability (rat hepatic microsomes), and little inhibition of hepatic CYP en...

Adrenal 20α-Hydroxysteroid Dehydrogenase in the Mouse Catabolizes Progesterone and 11-Deoxycorticosterone and Is Restricted to the X-Zone

Abstract: The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is a progesterone-catabolizing enzyme that is highly expressed in mouse ovaries and adrenals. Although the functional significance of ovarian 20alpha-HSD for the induction of parturition has been defined, regulation and distribution of 20alpha-HSD in the adrenal gland has not been determined. We demonstrate that the expression of adrenal 20alpha-HSD is restricted to the X-zone, a transient zone between the adrenal cortex and the medulla of yet unknown function. Adrenal 20alpha-HSD activity in male mice peaks at 3 wk of age and disappears thereafter, whereas 20alpha-HSD enzyme activity is maintained in adrenals from nulliparous female animals. Testosterone treatment of female mice induces rapid involution of the X-zone that is associated with the disappearance of the 20alpha-HSD-positive cells. Conversely, reappearance of 20alpha-HSD expression and activity in male animals is evident after gonadectomy. Moreover, pregnancy, but not pseudopregnancy, is accompanied by X-zone regression and loss of 20alpha-HSD activity. Pregnancy-induced X-zone regression and -abolished 20alpha-HSD expression is partially restored in animals that were kept from nursing their pups. We found that in addition to its progesterone-reducing activity, 20alpha-HSD also functions as an 11-deoxycorticosterone-catabolizing enzyme. The unaltered growth kinetics of the X-zone in 20alpha-HSD knockout animals suggests that 20alpha-HSD is not required for the regulation of X-zone growth. However, 20alpha-HSD expression and enzymatic activity in all experimental paradigms is closely correlated with the presence of the X-zone. These findings provide the basis for 20alpha-HSD as a reliable marker of the murine X-zone.