Disease relevance of Hsd17b1

• The presence of the type 1 17 beta HSD enzyme in fetal testes may explain the virilization of the mesonephric (Wolffian) duct which occurs in pseudohermaphrodite individuals lacking the type 3 isoform [1].
• This reaction is also catalyzed by type 3 17beta-HSD which is responsible for pseudohermaphroditism in deficient man but is asymptomatic in deficient women [2].
• The porcine FABGL (FabG (beta-ketoacyl-[acyl-carrierprotein] reductase, Escherichia coli) like) gene, coding for a 17beta-hydroxysteroid dehydrogenase (17beta-HSD), is a candidate gene for these traits [3].

Psychiatry related information on Hsd17b1

• Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model [4].

High impact information on Hsd17b1

• Only 144-hr preimplantation embryos were used to determine 17 beta-hydroxysteroid dehydrogenase (estradiol-17beta:NAD 17-oxidoreductase, EC 1.1.1.62) activity, which was present, suggesting synthesis of estrogen [5].
• 17-Ketosteroid reductase (17KSR), also known as 17 beta-hydroxysteroid dehydrogenase, catalyzes the reversible interconversion of estradiol to estrone and of androstenedione to testosterone [6].
• This epithelial-stromal interaction was specific for endometrial epithelial cells, since 17beta-HSD type 2 could not be induced in malignant breast epithelial cells by media conditioned with progestin-treated breast or endometrial stromal cells [7].
• These results suggest that progesterone- dependent paracrine factors arising from stromal cells are primarily responsible for the induction of epithelial 17beta-HSD type 2 expression in the endometrium [7].
• No progesterone response elements could be identified upstream of the 17beta-HSD type 2 promoter [7].

Biological context of Hsd17b1

• The open reading frame of the mouse 17 beta-HSD type-1 cDNA encodes a peptide of 344 amino acid residues with a predicted molecular mass of 36785 Da [8].
• Mouse type 5 17beta-HSD shares 76% amino acid sequence identity with human type 5 17beta-HSD; 71%, 76%, 76% with rat 3alpha-HSD and human types 1 and 3 3alpha-HSDs, respectively; and 71%, 69% and 77% with mouse, rat and human 20alpha-HSD, respectively [9].
• To determine more precisely the substrate specificity of the enzyme, we established a stable cell line expressing mouse type 5 17beta-HSD in transformed human embryonic kidney (293) cells [9].
• We searched expressed sequence tag databases with conserved domains of the short-chain alcohol dehydrogenase superfamily and identified another isoform of 17 beta-hydroxysteroid dehydrogenase, 17 beta HSDXI [10].
• The gene for 17 beta-hydroxysteroid dehydrogenase maps to human chromosome 17, bands q12-q21, and shows an RFLP with ScaI [11].

Anatomical context of Hsd17b1

• Consistent with steroidogenic enzyme activity, the testis of alphaERKO mice expressed higher steady state mRNA levels for steroidogenic acute regulatory protein and two enzymes involved in androgen biosynthesis, P450(17alpha) and 17beta-HSD type III, as determined by semiquantitative RT-PCR [12].
• Increased androgen biosynthesis by alphaERKO Leydig cells was associated with higher steroidogenic enzyme activity, especially of cytochrome P450 17alpha-hydroxylase/17-20 lyase (P450(17alpha)) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD), as measured by conversion of radiolabeled steroid substrates to T or its precursors [12].
• In the prostate, 17beta-HSD type 1 mRNA was exclusively found in the epithelial cells [13].
• In the pituitary gland of animals of both sexes, 17beta-HSD type 1 mRNA was expressed in the intermediate lobe melanotrophs while no specific signal could be detected in the anterior or posterior lobes of the pituitary [13].
• The present data indicate that E2 can be formed through the action of 17beta-HSD type 1 in specific cells of the gonads and peripheral tissues [13].

Associations of Hsd17b1 with chemical compounds

• The enzyme 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 catalyzes the conversion of estrone (E1) into 17beta estradiol (E2) [13].
• Thus, mouse 17 beta-HSD type 1 catalyzes reduction of androst-4-ene-3,17-dione (androstenedione) to 17 beta-hydroxyandrost-4-en-3-one (testosterone) as efficiently as 3 beta-hydroxyestra-1,3,5(10)-trien-17-one (estrone) to estra-1,3,5(10)-triene-3 beta, 17 beta-diol (estradiol) [8].
• The mouse enzyme type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD) catalyzes the conversion of androstenedione to testosterone and, to a lesser degree, the conversion of estrone to estradiol [14].
• The enzyme type 7 17beta-hydroxysteroid dehydrogenase (17beta-HSD) selectively catalyzes the conversion of estrone (E1) into estradiol (E2) [15].
• The purified enzyme was a 36-kDa monomer, and showed both 17beta-HSD and 3alpha-HSD activities in the presence of NADP(H) as the coenzymes [16].

Other interactions of Hsd17b1

• This activity seems to be specific to human, since mouse type 5 17beta-HSD does not show significant 20alpha-HSD activity [17].
• The properties of AKR1C20 are distinct from those of previously known mouse 17beta-HSD type 5 (AKR1C6), 3alpha-HSD (AKR1C14) and other members of the AKR1C subfamily [16].
• Although mRNA levels of 3beta-HSD and 17beta-HSD were unchanged, the P450scc mRNA level was significantly down-regulated by PCB126 in a dose-dependent manner [18].
• Since 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is the key enzyme in estradiol formation, the potent inhibitory effect of EM-800 on uterine 17beta-HSD could play an additional role by decreasing the availability of estradiol in the uterine tissue, while tamoxifen, on the contrary, stimulates activity of the enzyme [19].
• Types 1, 7, and 10 17beta-HSD, estrogen sulfotransferase type 1, and 11beta-HSD types 1 and 2 were found only in epithelial cells [20].

Analytical, diagnostic and therapeutic context of Hsd17b1

• Molecular cloning and characterization of mouse estradiol 17 beta-dehydrogenase (A-specific), a member of the aldoketoreductase family [21].
• To gain information about the cellular localization of 17beta-HSD mRNA type 1 expression, we performed in situ hybridization using a 35S-labeled cRNA probe in several tissues of adult mice of both sexes [13].

References