Disease relevance of HSD3B1

• OBJECTIVE: To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1 [1].
• Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility [2].
• The objective of the present study was to examine the potential impact of a T-->C substitution at codon Leu(338) of the type I (HSD3B1) 3 beta-HSD gene on obesity, circulating hormones, and estimates of insulin, glucose, and lipid metabolism as well as blood pressure in 284 unrelated Swedish men born in 1944 [3].

High impact information on HSD3B1

• However, evidence suggests that multiple signal transduction pathways are involved in IL-4 mediated HSD3B1 gene expression [4].
• The recent reports of a prostate cancer linkage at 1p13 provided additional evidence that HSD3B genes may be prostate cancer susceptibility genes [2].
• To evaluate the possible role of HSD3B genes in prostate cancer, we screened a panel of DNA samples collected from 96 men with or without prostate cancer for sequence variants in the putative promoter region, exons, exon-intron junctions, and 3'-untranslated region of HSD3B1 and HSD3B2 genes by direct sequencing [2].
• Transcription enhancer factor-5 and a GATA-like protein determine placental-specific expression of the Type I human 3beta-hydroxysteroid dehydrogenase gene, HSD3B1 [5].
• Instead, a 53-bp placental-specific enhancer element located between -2570 and -2518 of the HSD3B1 promoter was identified [5].

Chemical compound and disease context of HSD3B1

• 3beta-hydroxysteroid dehydrogenases (HSD3Bs), encoded by the HSD3B gene family at 1p13, have long been hypothesized to have a major role in prostate cancer susceptibility [2].

Biological context of HSD3B1

• Deletion and mutational analysis in transient transfections experiments revealed that contrarily to as previously shown for the HSD3B1 gene, lack of YY1 binding to the type II 3beta1-A element only results in a marginal reduction of basal promoter activity [6].
• The mRNA transcripts encoding CYP11A1 and HSD3B1, the enzymes for progesterone synthesis, were determined by quantitative real-time reverse transcription (RT)-PCR [7].
• Polymorphism in exon 4 of the human 3 beta-hydroxysteroid dehydrogenase type I gene (HSD3B1) and blood pressure [3].
• Other measurements such as BMI, WHR, abdominal sagittal diameter, salivary cortisol, total testosterone, serum leptin, fasting insulin and glucose, and serum lipids were not different across the HSD3B1 genotype groups [3].
• The HSD3B1 and HSD3B2 genes encoding the types I and II 3 beta-HSD isoenzymes, respectively, have been previously assigned by in situ hybridization to the chromosome 1p13.1 region [8].

Anatomical context of HSD3B1

• There was minimal expression of HSD3B1 and HSD3B2 (3beta-hydroxysteroid dehydrogenase I and II) in B-LCL and T cells [9].

Associations of HSD3B1 with chemical compounds

• These data provide strong evidence for the regulation of the 3 beta HSD-I and 17 beta HSD-II genes by cAMP and PKC and, thus, indicate an important endocrine and/or paracrine regulation of steroid hormone production in human placenta [10].
• The fasting glucose to insulin ratio in three of four PP girls with the descending HSD3B phenotype was lower than that in control PP girls, but one of four with the descending HSD3B phenotype had a higher fasting glucose to insulin ratio than the control PP girls [11].
• The adenovirus-mediated production of dominant-negative PRKAA totally abolished the effects of metformin on progesterone secretion, HSD3B and STAR protein production, and MAPK3/1 phosphorylation [12].
• Ketoconazole was without effect on the 3 beta-HSD-I and 17 beta-HSD activities when using [3H] pregnenolone and [3H] oestradiol, respectively, as substrates [13].
• Non-synonymous polymorphism in the coding sequence of human 3-beta hydroxysteroid dehydrogenase (HSD3B) [14].

Other interactions of HSD3B1

• Neither of the HSD3B1 or PTP1B variants were associated with HT [1].
• For other genes (HSD3B1, HSD3B2, HSD17B2), no information is available on these associations [15].
• CONCLUSIONS: Polymorphisms in HSD3B1, CYP19, AKR1C3 genes may be associated with an enlarged prostate in older men [16].
• The hormonal phenotype of Nonclassic 3 beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency [11].
• Its biochemical profile was similar to that of finasteride, whereas 4-MA (17 beta-N,N-diethyl-carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) was confirmed to be a non-selective 5 alpha-reductase inhibitor, showing a degree of binding affinity to the androgen receptor (RBA 0.1%) and a marked inhibition of 3 beta-HSD-I (IC50 32 nM) [17].

Analytical, diagnostic and therapeutic context of HSD3B1

• The subjects were genotyped by using PCR amplification of exon 4 of the HSD3B1 gene followed by digestion with the restriction enzyme BglII [3].
• The insulin sensitivity index determined by the frequently sampled iv glucose-tolbutamide test (FSIVGTT) in all HF with descending HSD3B phenotype and in all HF with classic PCOS, regardless of body mass index (BMI), was lower than in all eight normal BMI and five high BMI normal females [11].
• Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase [18].
• Site-directed mutagenesis provided the evidence that the 3 beta I-A element acts positively on the 3 beta-HSD-I gene promoter-mediated transcriptional activity upon transient transfection of both JEG-3 and SW13 cells [19].

References