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.

Subcellular concentrations of estrone, estradiol, androstenedione and 17β‐hydroxysteroid dehydrogenase (17‐β‐OH‐SDH) activity in malignant and non‐malignant human breast tissues

Abstract: Total and subcellular (cytosol and nuclear) concentrations of estrone (E1), estradiol (E2), and androstenedione were determined in non-malignant (n = 61) and malignant (n = 65) human breast tissues obtained from post-menopausal women. The 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH) activity was determined in 800g supernatant fraction. Total estrogens, E1 and E2 levels and 17 beta-OH-SDH activity were significantly (p less than 0.005, 0.0005, 0.001, respectively) higher in malignant than in non-malignant breast tissues. We failed to observe significant changes in subcellular steroid concentrations or enzyme activity associated with patients' obesity or tumor estrogen receptor status. When the steroid levels were analyzed in relation to clinical staging of the disease, nuclear contents of estradiol were significantly higher (p less than 0.005) in Stage-IV patients than in those with less advanced disease (Stages I to III). 17 beta-OH-SDH activity was significantly (p less than 0.001) lower in patients with advanced disease than in those with relatively less advanced (Stages I to III) disease and was positively correlated with tissue concentration of androstenedione. Our present data indicate that differential intracellular metabolism of steroid hormones may have some influence on availability of estradiol at nuclear sites. In postmenopausal women, local interconversion of estrogens may provide sufficient estrogenic stimulus to enhance the growth and progression of breast tumors.

Expression Patterns of 17β-Hydroxysteroid Dehydrogenase 14 in Human Tissues

Abstract: 17βHSD enzymes catalyze the stereospecific oxidation/reduction at carbon 17β of androgens and estrogens, and are important players in intracrine sex hormone synthesis. The biological relevance of 17βHSD14, first named retSDR3, is largely unknown. We generated and validated an antibody targeting the 17βHSD14 antigen and used this for immunohistochemical evaluation of expression patterns in 33 healthy human tissues. Furthermore, sex steroid conversional activity in HSD17B14 overexpressing HEK293 and MCF10A cells was investigated by assessing interconversion products of estrone, estradiol, androstenedione, testosterone, and dehydroepiandrosterone. Immunohistochemical staining patterns of 17βHSD14 with the enzyme being primarily expressed in glandular epithelial tissue reveal an enzyme with possible implications in the secretion or conversion of externally derived compounds. A role for 17βHSD14 in sex steroid metabolism is supported by the finding that 17HSD14 oxidizes both estradiol and testosterone into less bioactive steroid metabolites estrone and androstenedione, respectively.

Expression and kinetic properties of a recombinant 3α-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver

Abstract: Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

Some Biochemical Properties of Rabbit Ovarian Hydroxysteroid Dehydrogenases1

Abstract: An investigation was made of hydroxysteroid dehydrogenase activity in homogenates of rabbit ovaries from which the corpora lutea, if present, had been removed. Activity was determined by measuring the increase in optical density with time due to the formation of reduced pyridine nucleotide in incubation media saturated with oxidized pyridine nucleotide and hydroxysteroid. Activity was found toward steroids with hydroxyl groups in the 3β, 17β, 20α and 20β configurations. Both 3β- and 17β-hydroxysteroid dehydrogenase activities were stable for several days at either 3–5 or –20 C and were shown to.increase from pH 8.6 to 10.0. The 3β-hydroxysteroid dehydrogenase utilized DPN+ preferentially and was localized in the microsomal fraction, whereas the 17β-, 20α- and 20β-hydroxysteroid dehydrogenases preferred TPN+ and were found in the soluble fraction of an ovarian homogenate. The 3β-hydroxysteroid dehydrogenase activity (mμ/mole/ min/mg wet tissue) was found to be directly related to the weight of the ovary mi...