Редактирование: CYP17A1 (раздел)

==Publications==

{{medline-entry
|title=Intratumoral heterogeneity of the tumor cells based on in situ cortisol excess in cortisol-producing adenomas; ∼An association among morphometry, genotype and cellular senescence∼.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33002589
|abstract=Cortisol-producing adrenocortical adenomas (CPAs) are associated with ACTH-independent Cushing's syndrome and histologically composed of two cellular subtypes: compact (lipid-poor) and clear (lipid-rich) tumor cells. However, the details of hormonal and biological activities of these tumor cells have remained unknown, especially in CPAs. CPAs frequently harbored unique histological features different from those of aldosterone-producing adenomas (APAs) including a senescent phenotype. Therefore, we explored the association between morphological features and the immunoreactivity of steroidogenic enzymes in CPAs with different genotypes and compared them with cellular senescence markers as well as clinicopathological factors of the cases. Hormonal activities (3βHSD, CYP21A, [[CYP17A1]], [[CYP11B1]] and DHEA-ST) and cellular senescence markers (p16, p21 and Ki-67) within different morphological features (clear and compact) were evaluated in 40 CPAs. CPA genotypes ([[PRKACA]], [[[[[[[[GNAS]]]]]]]] and CTNNB1) were examined by Sanger sequencing and then compared them with the factors above. p21 immunoreactivity was significantly positively correlated with that of CYP21A (p = 0.0110), [[CYP17A1]] (p = 0.0356) and DHEA-ST (p = 0.0420) but inversely with tumor size (p = 0.0015). CYP21A (p = 0.0016), [[CYP11B1]] (p = 0.0001), [[CYP17A1]] (p < 0.0001) and p16 (p = 0.0137) immunoreactivity were all significantly higher in compact cells than those in clear cells. [[CYP17A1]] (p = 0.0056) and 3βHSD (p = 0.0437) immunoreactivity was significantly higher in [[PRKACA]]-mutated than wild type CPAs. p16 immunoreactivity and serum DHEA-S level were both significantly higher in [[[[[[[[GNAS]]]]]]]]-mutated than [[PRKACA]]-mutated (p = 0.0250) and wild type (p = 0.0180) CPAs. Results of our present study did demonstrate that compact tumor cells were hormonally active and more senescent than clear tumor cells in CPAs. [[PRKACA]]- and [[[[[[[[GNAS]]]]]]]]-mutated tumor cells were more hormonally active and senescent than those without mutations despite the similar morphological features. We herein proposed a novel histological classification of the tumor cell subtypes based on in situ cortisol excess, genotypes and the status of cell senescence in CPAs.

|keywords=* CYP11B1
* CYP17A
* Cellular senescence
* Compact and clear cells
* Cortisol-producing adenoma
* PRKACA
|full-text-url=https://sci-hub.do/10.1016/j.jsbmb.2020.105764
}}
{{medline-entry
|title=Combined toxicity of endosulfan and phenanthrene mixtures and induced molecular changes in adult Zebrafish (Danio rerio).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29197246
|abstract=Individual and combined toxicities of endosulfan (ENDO) with phenanthrene (PHE) were evaluated using zebrafish (Danio rerio) adults. The 96-h LC  values for ENDO and PHE were 4.6 μg L  and 920 μg L , respectively. To evaluate the mixture toxicity, LC  and LC  concentrations were grouped into four combinations as ENDO-LC    PHE-LC , ENDO-LC    PHE-LC , ENDO-LC    PHE-LC , and ENDO-LC    PHE-LC , and their acute toxicities were determined. The combination of LC -ENDO and LC -PHE exhibited a synergistic effect. In addition, acetylcholinesterase activity decreased in zebrafish bodies exposed to ENDO with or without PHE. Combined treatments induced higher glutathione S-transferase activity compared to individual treatments. Carboxylesterase activity increased in both heads and bodies of ENDO-treated fishes compared with PHE-treated fishes. Using RT-qPCR technique, CYP1A gene expression significantly up-regulated in all combinations, whereas CYP3A was unchanged, suggesting that enzymes involved in defense may play different roles in the detoxification. [[CYP7A1]] gene responsible for bile acid biosynthesis is dramatically down-regulated after exposure to the synergistic combination exposure, referring that the synergistic effect may be resulted from the reduction of bile production in zebrafishes. Among gender-related genes, [[CYP11A1]] and [[CYP17A1]] genes in female zebrafish decreased after treatment with ENDO alone and combination of LC -ENDO and LC -PHE. This might be related to a reduction in cortisol production. The overall results indicated that ENDO and PHE were toxic to zebrafish adults both individually and in combination, and that their co-presence induced changes in the expression of genes responsible for metabolic processes and defense mechanisms.
|mesh-terms=* Acetylcholinesterase
* Aging
* Animals
* Carboxylesterase
* Cytochrome P-450 Enzyme System
* Drug Synergism
* Endosulfan
* Female
* Glutathione Transferase
* Insecticides
* Male
* Phenanthrenes
* Water Pollutants, Chemical
* Zebrafish
|keywords=* Endosulfan
* Enzyme activity
* Gene expression
* Mixture toxicity
* Phenanthrene
* Zebrafish
|full-text-url=https://sci-hub.do/10.1016/j.chemosphere.2017.11.128
}}
{{medline-entry
|title=Testicular gene expression of steroidogenesis-related factors in prepubertal, postpubertal, and aging dogs.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28166986
|abstract=Developmental and aging changes in testicular factors related to steroidogenesis are unknown in dogs. Using reverse transcription quantitative real-time PCR, this study examined testicular mRNA levels of [[CYP11A1]] (P450 cholesterol side-chain cleavage enzyme, P450scc), [[CYP17A1]] (P450 17α-hydroxylase/C17-20 lyase, P450c17), [[HSD3B2]] (3β-hydroxysteroid dehydrogenase, 3β-HSD), CYP19A (P450 aromatase, P450arom), [[STAR]] (steroidogenic acute regulatory protein, StAR), cyclooxygenase (COX) -1 and COX-2 in prepubertal (4-6 months of age), postpubertal (1 year of age), and aging (2-18 years of age) dogs. Testicular mRNA levels for P450scc, 3β-HSD, StAR, COX-1, and COX-2 did not change from prepubertal to postpubertal stages, whereas that for P450arom markedly and abruptly increased and that for P450c17 gradually decreased. In postpubertal and aging dogs, a negative correlation was found between aging and testicular P450arom mRNA levels. Based on the rapid testicular growth observed during puberty, these results suggested that total testis gene expression for steroidogenesis-related factors, in particular for P450arom, increases during puberty in dogs. In addition, the decline in P450arom gene expression during aging may affect the ability to synthesize steroids in canine testes.
|mesh-terms=* 3-Hydroxysteroid Dehydrogenases
* Aging
* Animals
* Aromatase
* Cholesterol Side-Chain Cleavage Enzyme
* Cyclooxygenase 1
* Cyclooxygenase 2
* Dogs
* Gene Expression Regulation, Developmental
* Male
* Phosphoproteins
* RNA, Messenger
* Steroid 17-alpha-Hydroxylase
* Testis
|keywords=* Aging
* Dog
* Puberty
* Steroidogenesis
* Testis
|full-text-url=https://sci-hub.do/10.1016/j.theriogenology.2016.11.007
}}
{{medline-entry
|title=[[CYP17A1]] Enzyme Activity Is Linked to Ambulatory Blood Pressure in a Family-Based Population Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26297028
|abstract=Genome-wide association studies have linked [[CYP17A1]] coding for the steroid hormone synthesizing enzyme 17α-hydroxylase ([[CYP17A1]]) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent [[CYP17A1]] activity in a family-based population study and estimated the heritability of [[CYP17A1]] activity. In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. [[CYP17A1]] activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed [[CYP17A1]] activities exploring effect modification by urinary sodium excretion. Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night [[CYP17A1]] activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). [[CYP17A1]] activities, assessed with ratio 1, were lower in older participants. Low apparent [[CYP17A1]] activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. [[CYP17A1]] activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of [[CYP17A1]] with BP.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Biomarkers
* Blood Pressure
* Blood Pressure Monitoring, Ambulatory
* Circadian Rhythm
* Cross-Sectional Studies
* Female
* Gene-Environment Interaction
* Genetic Association Studies
* Genotype
* Heredity
* Humans
* Hypertension
* Male
* Middle Aged
* Natriuresis
* Phenotype
* Risk Factors
* Sodium
* Sodium Chloride, Dietary
* Steroid 17-alpha-Hydroxylase
* Steroids
* Substrate Specificity
* Switzerland
* Time Factors
* Urinalysis
* Young Adult
|keywords=* CYP17A1
* aging
* blood pressure
* heritability
* hypertension
* salt
* steroids.
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886492
}}
{{medline-entry
|title=Sequence analysis of six blood pressure candidate regions in 4,178 individuals: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25275628
|abstract=Genome-wide association studies (GWAS) identified multiple loci for blood pressure (BP) and hypertension. Six genes--ATP2B1, CACNB2, [[CYP17A1]], JAG1, PLEKHA7, and SH2B3--were evaluated for sequence variation with large effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Targeted genomic sequence was determined in 4,178 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Common variants (≥50 minor allele copies) were evaluated individually and rare variants (minor allele frequency, MAF≤1%) were aggregated by locus. 464 common variants were identified across the 6 genes. An upstream [[CYP17A1]] variant, rs11191416 (MAF = 0.09), was the most significant association for SBP (P = 0.0005); however the association was attenuated (P = 0.0469) after conditioning on the GWAS index single nucleotide polymorphism (SNP). A PLEKHA7 intronic variant was the strongest DBP association (rs12806040, MAF = 0.007, P = 0.0006) and was not in LD (r² = 0.01) with the GWAS SNP. A CACNB2 intronic SNP, rs1571787, was the most significant association with PP (MAF = 0.27, P = 0.0003), but was not independent from the GWAS SNP (r² = 0.34). Three variants (rs6163 and rs743572 in the [[CYP17A1]] region and rs112467382 in PLEKHA7) were associated with BP traits (P<0.001). Rare variation, aggregately assessed in the 6 regions, was not significantly associated with BP measures. Six targeted gene regions, previously identified by GWAS, did not harbor novel variation with large effects on BP in this sample.
|mesh-terms=* Aging
* Blood Pressure
* Cohort Studies
* Heart
* Humans
* Sequence Analysis

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183565
}}
{{medline-entry
|title=Of mice and men--warning: intact versus castrated adult male mice as xenograft hosts are equivalent to hypogonadal versus abiraterone treated aging human males, respectively.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23775398
|abstract=Immune deficient male mice bearing human prostate cancer xenografts are used to evaluate therapeutic response to novel androgen ablation approaches and the results compared to surgical castration based upon assumption that testosterone microenvironment in intact and castrated adult male mice mimics eugonadal and castrated aging adult human males. To test these assumptions, serum total testosterone (TT) and free testosterone (FT) were determined longitudinally in groups (n > 20) of intact versus castrated adult male nude, [[NOG]], and immune competent C57BL/6 mice. In adult male mice, TT and FT varies by 30- to 100-fold within the same animal providing a microenvironment that is only equivalent to hypogonadal, not eugonadal, adult human males (TT is 1.7 ± 1.2 ng/ml [5.8 ± 4.1 nM] in nude and 2.5 ± 1.3 ng/ml [8.7 ± 4.4 nM] in [[NOG]] mice versus >4.2 ng/ml [14.7 nM] in eugonadal humans). This was confirmed based upon enhanced growth of androgen dependent human prostate cancer xenografts inoculated into mice supplemented with exogenous testosterone to elevate and chronically maintain serum TT at a level (5 ng/ml [18 nM]) equivalent to a 50-year-old eugonadal human male. In castrated mice, TT and FT range from 2 to 20 pg/ml (7-70 pM) and <0.8 pg/ml (<2.6 pM), respectively, which is equivalent to castrate resistant prostate cancer (CRPC) patients treated with abiraterone. This was confirmed based upon the inability of another [[CYP17A1]] inhibitor, ketoconazole, to inhibit the growth of CRPC xenografts in castrated mice. Adult male mice supplemented with testosterone mimic eugonadal human males, while unsupplemented animals mimic standard androgen ablation and castrated animals mimic abiraterone treated patients. These studies confirm what is claimed in Robert Burns' poem "To a Mouse" that "The best laid schemes of mice and men/often go awry.".
|mesh-terms=* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Androstenes
* Androstenols
* Animals
* Cell Line, Tumor
* Humans
* Hypogonadism
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Nude
* Middle Aged
* Orchiectomy
* Testosterone
* Xenograft Model Antitumor Assays
|keywords=* eugonadal levels
* free testosterone
* hypogonadal levels
* mice versus humans
* serum total testosterone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009979
}}
{{medline-entry
|title=Perimenopausal regulation of steroidogenesis in the nonhuman primate.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21683476
|abstract=Human aging is characterized by a marked decrease in circulating levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), hormonal changes associated with cognitive decline. Despite beneficial effects of DHEA supplementation in rodents, studies in elderly humans have generally failed to show cognitive improvement after treatment. In the present study we evaluate the effects of age and estradiol supplementation on expression of genes involved in the de novo synthesis of DHEA and its conversion to estradiol in the rhesus macaque hippocampus. Using reverse transcription polymerase chain reaction (RT-PCR) we demonstrate the expression of genes associated with this synthesis in several areas of the rhesus brain. Furthermore, real-time PCR reveals an age-related attenuation of hippocampal expression level of the genes [[CYP17A1]], [[STS]], and 3BHSD1/2. Additionally, short-term administration of estradiol is associated with decreased expression of [[CYP17A1]], [[STS]], [[SULT2B1]], and AROMATASE, consistent with a downregulation not only of estrogen synthesis from circulating DHEA, but also of de novo DHEA synthesis within the hippocampus. These findings suggest a decline in neurosteroidogenesis may account for the inefficacy of DHEA supplementation in elderly humans, and that central steroidogenesis may be a function of circulating hormones and menopausal status.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Dehydroepiandrosterone
* Estradiol
* Female
* Hippocampus
* Hydrocortisone
* Macaca mulatta
* Male
* Perimenopause
* Primates

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196783
}}
{{medline-entry
|title=Genetic variation in sex hormone genes influences heel ultrasound parameters in middle-aged and elderly men: results from the European Male Aging Study (EMAS).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18767927
|abstract=Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in [[AR]], [[ESR1]], [[ESR2]], [[CYP19A1]], [[CYP17A1]], [[SHBG]], [[SRD5A2]], [[LHB]], and [[LHCGR]]. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1  /- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0  /- 18.9 dB/Mhz, SOS was 1550.2  /- 34.1 m/s, and BMD was 0.542  /- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within [[CYP19A1]], peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta =-0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in [[AR]] and SNPs in [[CYP17A1]], [[LHCGR]], and [[ESR1]]. Our data confirm evidence of association between bone QUS parameters and polymorphisms in [[CYP19A1]], as well as modest associations with polymorphisms in [[CYP17A1]], [[ESR1]], [[LHCGR]], and [[AR]] in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.
|mesh-terms=* Aged
* Aging
* Aromatase
* Bone Density
* Calcaneus
* European Continental Ancestry Group
* Genetic Variation
* Genotype
* Gonadal Steroid Hormones
* Humans
* Male
* Middle Aged
* Polymorphism, Genetic
* Repetitive Sequences, Nucleic Acid
* Ultrasonography

|full-text-url=https://sci-hub.do/10.1359/jbmr.080912
}}