Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 48 tissue specimens of human female breast cancer and, in addition, 48 nonmalignant tissue specimens obtained in each case from the same cancer-bearing breast. In all cases the nonmalignant tissue showed greater conversion of estradiol-17 beta into estrone than the neoplastic tissues. In normal human breast tissue of premenopausal women specific enzyme activity depended on the phase of the MENSTRUAL CYCLE: the highest values of 17 beta-HSD activity were found in the early secretory phase. To determine the intracellular distribution of the 17 beta-HSD, purified microsomes, mitochondria, peroxysomes, lysosomes, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the 17 beta-HSD was mainly located in mitochondria and microsomes. Furthermore it could be demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17 beta-HSD was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements and maximal velocities) of a cytoplasmic, nuclear, mitochondrial and microsomal 17 beta-HSD of normal and neoplastic human mammary tissue were compared. Maximal velocity was highest in enzyme preparations of normal mammary tissue obtained from premenopausal women in the early secretory phase. Km-values wrere nearly identical in normal and neoplastic mammary tissue preparations (approx. 1 X 10(-6) M). NAD was more efficient than NADP as a cofactor. For the conversion of estradiol to estrone the optimum temperature was approximately 40 degrees C and the optimum pH 9.5. For the reduction of estrone the optimum pH was 6.5. Sulphydryl groups were shown to be essential for catalysis.
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PMID:Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue. 1 41

Microsomal 17 beta-hydroxysteroid dehydrogenase obtained from the human secretory endometrium (17 beta-HSD) was solubilized with triton X-100. A 4-fold purification was achieved by ammonium sulphate precipitation and isoelectric focusing. In the presence of glycerol the partially purified enzyme was stable at 4 degrees C for at least 48 h. Using crude microsomes, the conversion of oestradiol to oestrone was linear with time and with the concentration of protein. The optimum temperature was approximately 40 degrees C and the optimum pH 9.4. For the reduction of oestrone the optimum pH was 6.5. With NAD, oestradiol was oxidized approximately three times more rapidly than with NADP. Km-values for oestradiol were nearly the same in endometrial carcinoma and in proliferative and secretory endometrium (i.e. approximately 3 X 10(-6) M). The maximal velocity was highest in secretory endometrium. Testosterone and androstenedione could also serve as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis.
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PMID:Studies on 17 beta-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. III. Partial purification and characterization of the microsomal enzyme. 24 Nov 86

The ovary of the domestic pigeon, Columba livia, has been assayed histochemically for the localization of delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSDH), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSDA), 11 beta-hydroxysteroid dehydrogenase (11 beta-HSDH), glucose-6-phosphate dehydrogenase (G6P-DH) and NADH-diaphorase activities during different periods of the reproductive cycle. delta 5-3 beta-HSDH, 17 beta-HSDH, 11 beta-HSDH, G6P-DH and NADH-diaphorase activity was found in the theca interna of growing, atretic and postovulatory follicles, the granulosa of ovulatory, atretic and postovulatory follicles, and interstitial gland cells during the pre-incubation and the laying periods. During the incubation and squab feeding periods only delta 5-3 beta-HSDH, G6P-DH and NADH-diaphorase activities were observed in the above mentioned cells. The steroidogenic potential of atretic follicles depends upon the type of atresia a follicle undergoes.
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PMID:Steroid synthesizing cellular sites in the ovary of the domestic pigeon Columba livia (Gmelin): a histochemical study. 45 38

Transient expression in nonsteroidogenic mammalian cells of the rat wild type I and type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) cDNAs shows that the encoded proteins, in addition to being able to catalyze the oxidation and isomerization of delta 5-3 beta-hydroxysteroid precursors into the corresponding delta 4-3-ketosteroids, interconvert 5 alpha-dihydrotestosterone (DHT) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol). When homogenate from cells transfected with a plasmid vector containing type I 3 beta-HSD is incubated in the presence of DHT using NAD+ as cofactor, a somewhat unexpected metabolite is formed, namely 5 alpha-androstanedione (A-dione), thus indicating an intrinsic androgenic 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity of this 3 beta-HSD isoform. Although the relative Vmax of 17 beta-HSD activity is 14.9-fold lower than that of 3 beta-HSD activity, the Km value for the 17 beta-HSD activity of type I 3 beta-HSD is 7.97 microM, a value which is in the same range as the conversion of DHT into 3 beta-diol which shows a Km value of 4.02 microM. Interestingly, this 17 beta-HSD activity is highly predominant in unbroken cells in culture, thus supporting the physiological relevance of this "secondary" activity. Such 17 beta-HSD activity is inhibited by the classical substrates of 3 beta-HSD, namely pregnenolone (PREG), dehydroepiandrosterone (DHEA), delta 5-androstene-3 beta,17 beta-diol (delta 5-diol), 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) and DHT, with IC50 values of 2.7, 1.0, 3.2, 6.2, and 6.3 microM, respectively. Although dual enzymatic activities have been previously reported for purified preparations of other steroidogenic enzymes, the present data demonstrate the multifunctional enzymatic activities associated with a recombinant oxidoreductase enzyme. In addition to its well known 3 beta-HSD activity, this enzyme possesses the ability to catalyze DHT into A-dione thus potentially controlling the level of the active androgen DHT in classical steroidogenic as well as peripheral intracrine tissues.
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PMID:Androgenic 17 beta-hydroxysteroid dehydrogenase activity of expressed rat type I 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase. 130 51

In human placenta the enzyme complex aromatase catalyzes the conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates the reversible interconversion of, e.g. estrone to estradiol. We studied the effects of cholera toxin (CT), an activator of adenylate cyclase, and 12-O-tetradecanoyl phorbol 13-acetate (TPA), a phorbol ester protein kinase C activator, on the levels of messenger (m) RNAs encoding aromatase cytochome P-450 (P-450AROM) and 17 beta-HSD in cultured JEG-3 choriocarcinoma cells. With the use of oligonucleotide probes designed according to known complementary DNA sequences, hybridizable mRNA transcripts of 3.0, 2.4, and 1.6 kilobases for P-450AROM were found in Northern blot analysis of JEG-3 cell RNA. A single 1.4-kilobase transcript was detected for 17 beta-HSD. Time-dependent increases in P-450AROM mRNA levels in JEG-3 cells were observed for both CT and TPA with maximal effects at 24-48 h. CT and TPA increased P-450AROM mRNA levels in a concentration-dependent manner. The maximal effects, about 4.8-fold and 3.3-fold stimulations above basal levels, were obtained with 10 ng/ml of CT and 100 ng/ml of TPA, respectively. The effects of CT and TPA were additive. CT induced 17 beta-HSD mRNA levels in a time- and concentration-dependent manner and its maximal effect of 10.1-fold above basal levels was obtained within a similar time and concentration-dependence as for P-450AROM mRNA. TPA itself had no clear effect but it approximately doubled the effect of CT on 17 beta-HSD mRNA expression. Inhibition of protein synthesis by cycloheximide decreased basal, CT and TPA stimulated P-450AROM mRNA levels but increased the expression of 17 beta-HSD mRNA. This result is consistent with the hypothesis that induction of P-450AROM gene expression is mediated by a labile protein regulator resembling to most other steroidogenic P-450 enzymes, whereas 17 beta-HSD as a non-P450 enzyme appears to be controlled in a different manner. The present results suggest that: 1) induction of P-450AROM mRNA may at least partly be responsible for our previously reported increases in the rate of conversion of androgens to estrogens by CT and TPA in JEG-3 cells; 2) 17 beta-HSD mRNA expression is mainly controlled through a cAMP-dependent mechanism in contrast to the multifactorial control of P-450AROM mRNA; and 3) protein synthesis inhibition by cycloheximide has opposite effects on the mRNA levels of these two key enzymes in placental estrogen metabolism.
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PMID:Regulation of aromatase cytochrome P-450 and 17 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels in choriocarcinoma cells. 130 52

The interconversion of estrone (E1) and 17 beta-estradiol (E2), androstenedione (4-ene-dione) and testosterone (T), as well as dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol is catalyzed by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD). The enzyme 17 beta-HSD thus plays an essential role in the formation of all active androgens and estrogens in gonadal as well as extragonadal tissues. The present study investigates the tissue distribution of 17 beta-HSD activity in the male and female rat as well as in some human tissues and the distribution of 17 beta-HSD mRNA in some human tissues. Enzymatic activity was measured using 14C-labeled E1, E2, 4-ene-dione and T as substrates. Such enzymatic activity was demonstrated in all 17 rat tissues examined for both androgenic and estrogenic substrates. While the liver had the highest level of 17 beta-HSD activity, low but significant levels of E2 as well as T formation were found in rat brain, heart, pancreas and thymus. The oxidative pathway (E2----E1, T----4-ene-dione) was favored over the reverse reaction in almost all rat tissues while in the human, almost equal rates were found in most of the 15 tissues examined. The widespread distribution of 17 beta-HSD in rat and human tissues clearly indicates the importance of this enzyme in peripheral sex steroid formation or intracrinology.
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PMID:Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. 131 80

The insert of 1278 bp containing the entire coding region of cDNA encoding human 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was inserted into a pHS1 vector and expressed in HeLA human cervical carcinoma cells and COS-1 monkey kidney tumor cells. Western blot analysis indicated that the expressed protein migrates at the same position as the purified enzyme and is recognized by the antibody raised against purified human placental 17 beta-HSD. The expressed enzyme efficiently catalyzes the interconversion of estrone and estradiol while dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol are interconverted at a lower rate. The present data suggest the existence of two 17 beta-HSDs.
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PMID:Expression of human 17 beta-hydroxysteroid dehydrogenase in mammalian cells. 131 81

Primates are unique in having adrenals that secrete large amounts of the precursor sex steroids (PSS) dehydroepiandrosterone (DHEA) and especially DHEA-sulfate. The adrenal PSS require the action of 3 beta-hydroxysteroid dehydrogenase/5-ene-4 ene isomerase (3 beta-HSD), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), 5 alpha-reductase and/or aromatase to form the androgen dihydrotestosterone (DHT) or the estrogens 17 beta-estradiol and androst-5-ene-diol. Knowing the crucial role of 3 beta-HSD and 17 beta-HSD in sex steroid biosynthesis both in classical as well as in peripheral steroidogenic tissues, we have concentrated our efforts on the elucidation of the molecular structure of these enzyme families. We have thus characterized two types of human 3 beta-HSD cDNA clones and their corresponding genes which encode deduced proteins of 371 and 372 amino acids and share 93.5% homology. Human type I 3 beta-HSD is the almost exclusive mRNA species expressed in the placenta and skin, while human type II is the predominant mRNA species in the adrenals, ovaries and testes. We have also recently elucidated the structure of three types of rat 3 beta-HSD cDNAs which all encode a 372 amino acid protein. The predicted rat type I and II 3 beta-HSD proteins expressed adrenals, gonads and adipose tissue share 94% homology while they share 80% similarity with the liver-specific type III 3 beta-HSD. Transient expression of human type I and II as well as rat type I and II 3 beta-HSD cDNAs in HeLa human cervical carcinoma cells reveals that 3 beta-ol dehydrogenase and 5-ene-4-ene isomerase activities reside within a single protein and that these cDNAs encode functional 3 beta-HSD proteins. The expressed rat type III protein possesses a unique property catalyzing selectively the reduction of 3 beta-androstane 5 alpha-steroids such as DHT. Furthermore, we have also demonstrated by site-directed mutagenesis that the lower activity of expressed rat type II compared to rat type I 3 beta-HSD protein is due to a change of four amino acid residues potentially involved in a membrane-spanning domain. In parallel, we have characterized the complete nucleotide sequence of human 17 beta-HSD cDNA clones encoding a 327 amino acid protein as well as two in tandem 17 beta-HSD genes. Two major 17 beta-HSD mRNA species have been detected in several tissues due to a tissue-specific alternative site of initiation of transcription.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ontogeny and subcellular localization of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the human and rat adrenal, ovary and testis. 139 Feb 95

The metabolism of testosterone in the rat ventral prostate, anterior pituitary, basal hypothalamus and amygdala was studied in vitro under the influence of vitamin B6 compounds. The influence of these compounds on the activity of 5 alpha-reductase (5 alpha-R), 3 alpha- and 17 beta-hydroxysteroid dehydrogenase (3 alpha-HSD, 17 beta-HSD) was determined for all the examined tissues. Pyridoxine hydrochloride significantly increased the activity of 5 alpha-R, 3 alpha- and 17 beta-HSD, but pyridoxal hydrochloride had an inhibitory influence on 5 alpha-R and showed no effect on 3 alpha-HSD activity at the prostate level. Male rat anterior pituitary, basal hypothalamus or amygdala incubated with pyridoxal phosphate and pyridoxal hydrochloride showed modified enzymatic activities. Pyridoxal hydrochloride showed an inhibitory effect on 5 alpha-R in the rat pituitary and basal hypothalamus as well as in the rat prostate.
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PMID:Androgen hydroxysteroid dehydrogenases under the influence of pyridoxine derivatives. 142 Dec 8

Blood cells of male and female rainbow trout showed 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity in vitro, reducing 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione (OA) to 11 beta-hydroxytestosterone and 11-ketotestosterone (OT), respectively. Enzyme activity did not vary with gonadal development in either sex. The conversion of tritiated precursors was partly inhibited in the presence of steroid-free serum or radioinert steroid, but inhibition was less strong when radioinert androgens were added to steroid-free serum or when the serum contained endogenous steroids. Treatment of male trout with salmon gonadotropin in vivo and/or incubation with a pituitary extract of mature salmon in vitro did not affect OA conversion when blood cells were incubated in the absence of serum, whereas it was slightly but significantly higher when they were incubated in the presence of serum and pituitary extract. In addition to blood cells and steroidogenic tissues, spleen, intestine, brain, liver, excretory kidney, and skin tissue also produced an OA metabolite isopolar to OT in vitro, so that 17 beta HSD appears to be present in a variety of trout issues. With respect to the biological significance of extragonadal steroid metabolism in vivo, the ligand binding characteristics of circulating steroid binding proteins may be of primary relevance in regulating substrate availability.
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PMID:Extragonadal 17 beta-hydroxysteroid dehydrogenase activity in rainbow trout. 164 80


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