HSD17B8 Human
Description
Biochemical Characteristics and Enzymatic Activities
HSD17B8 exhibits both oxidative and reductive catalytic activities, depending on substrate and cellular context. Key features include:
Table 1: Comparative Activity of 17β-HSD Isoenzymes
| Isoenzyme | Primary Function | Preferred Substrates | Cofactor | Tissue Expression |
|---|---|---|---|---|
| HSD17B1 | Estrogen activation | Estrone → Estradiol | NADPH | Ovary, breast, placenta |
| HSD17B2 | Androgen/estrogen inactivation | Estradiol → Estrone | NAD⁺ | Liver, prostate, endometrium |
| HSD17B8 | Dual oxidative/reductive | E2 ↔ E1, testosterone → androstenedione | NAD⁺ | Prostate, kidney, brain, ovary |
Physiological Roles in Steroid Metabolism
HSD17B8 regulates the balance of biologically active and inactive steroids:
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Oxidative Activity: Predominantly inactivates E2, testosterone, and DHT, reducing their receptor-binding capacity .
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Reductive Activity: Converts E1 to E2 under specific conditions, contributing to local estrogen synthesis .
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Fatty Acid Biosynthesis: May participate in mitochondrial fatty acid metabolism via 3-oxoacyl-[acyl-carrier-protein] reductase activity .
Key Pathways Involving HSD17B8
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Estrogen Metabolism
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Androgen Inactivation
Clinical and Pathological Implications
HSD17B8’s expression levels correlate with disease outcomes and therapeutic responses:
Table 2: HSD17B8 Expression in Tissues and Disease States
Research Findings and Therapeutic Targets
Recent studies highlight HSD17B8’s dual role in cancer and metabolism:
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Breast Cancer Prognosis:
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Fatty Acid Biosynthesis:
Key Studies
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PTEN-HSD17B8 Interaction:
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Breast Cancer Biomarker:
Product Specs
E2 17-beta-dehydrogenase 8, 17-beta-hydroxysteroid dehydrogenase 8, 17-beta-HSD 8, 3-oxoacyl-[acyl-carrier-protein] reductase, Protein Ke6, Ke-6, Really interesting new gene 2 protein, Testosterone 17-beta-dehydrogenase 8, HSD17B8, FABGL, HKE6, RING2, KE6, FABG, H2-KE6, SDR30C1, D6S2245E, dJ1033B10.9.
Q&A
HSD17B8 Research FAQs
Advanced Research Questions
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How do environmental toxins alter HSD17B8 expression, and what are the experimental models to study this?
Key findings and methods:
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Arsenic exposure decreases HSD17B8 mRNA in hepatic cells (IC₅₀ = 5 μM, 24h exposure) .
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Phthalates (e.g., dibutyl phthalate) upregulate expression in reproductive tissues (2-fold increase, p < 0.01) .
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Experimental models:
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What conflicting data exist regarding HSD17B8’s role in cancer, and how can they be resolved?
Contradictions include:
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Pro-cancer effects: Cisplatin upregulates HSD17B8 in ovarian cancer cells (A2780 line, 3.5-fold increase) .
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Anti-cancer effects: HSD17B8 knockdown increases breast cancer cell (MCF-7) proliferation by 40% .
Resolution strategies: -
Use isogenic cell lines to control for genetic background.
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Perform pathway enrichment analysis (e.g., KEGG) to identify context-dependent interactors .
Data Tables
Table 1: HSD17B8 Response to Chemical Exposure
Table 2: HSD17B8 Expression in Human Cancers
| Cancer Type | Expression Trend | Prognostic Association | Dataset | Source |
|---|---|---|---|---|
| Breast adenocarcinoma | ↓ | Poor survival (HR=1.8) | TCGA-BRCA | |
| Ovarian serous cyst | ↑ | Chemoresistance | CPTAC-OV |
Methodological Guidance
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How to design a study investigating HSD17B8’s role in metabolic disorders?
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Cohort selection: Prioritize patients with dyslipidemia or type 2 diabetes (n ≥ 100 for 80% power) .
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Endpoint assays:
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Controls: Age/BMI-matched healthy subjects; HSD17B8 KO mice for preclinical validation .
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What computational tools predict HSD17B8’s interaction networks?
Product Science Overview
The HSD17B8 gene is located on chromosome 6 and encodes a protein that is approximately 261 amino acids in length . The protein structure includes a conserved NAD(P)-binding domain, which is characteristic of the SDR family . This domain is essential for the enzyme’s catalytic activity, allowing it to participate in redox reactions involving steroid hormones .
HSD17B8 primarily functions as an oxidative enzyme, inactivating potent steroid hormones such as estradiol, testosterone, and dihydrotestosterone by converting them into their less active forms . Specifically, it catalyzes the conversion of estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to androstanedione . Although its primary role is oxidative, HSD17B8 also exhibits some reductive activity, enabling it to convert estrone back to estradiol under certain conditions .
The regulation of steroid hormone levels by HSD17B8 is vital for maintaining hormonal balance and ensuring proper physiological function. In particular, the enzyme’s activity is crucial in tissues where precise control of estrogen and androgen levels is necessary, such as the ovaries, testes, liver, pancreas, and kidneys . Dysregulation of HSD17B8 activity can lead to hormonal imbalances and has been associated with various diseases, including certain types of cancer .
Mutations or alterations in the HSD17B8 gene can have significant clinical implications. For instance, changes in the enzyme’s activity have been linked to conditions such as Fallopian Tube Serous Papilloma . Understanding the function and regulation of HSD17B8 is therefore important for developing therapeutic strategies for diseases related to steroid hormone imbalances.
Recombinant HSD17B8 refers to the enzyme produced through recombinant DNA technology, which involves inserting the HSD17B8 gene into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant form is used in research to study the enzyme’s structure, function, and potential therapeutic applications. It allows scientists to investigate the enzyme’s role in steroid metabolism and its impact on various physiological processes.
