The 11β-hydroxyandrostenedione pathway and C11-oxy C21 backdoor pathway are active in benign prostatic hyperplasia yielding 11keto-testosterone and 11keto-progesterone

Publication date: Available online 15 October 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Therina du Toit, Amanda C. SwartAbstractIn clinical approaches to benign prostatic hyperplasia (BPH) and prostate cancer (PCa), steroidogenesis or the disruption thereof is the main thrust in treatments restricting active androgen production. Extensive studies have been undertaken focusing on testosterone and dihydrotestosterone (DHT). However, the adrenal C11-oxy C19 steroid, 11β-hydroxyandrostenedione (11OHA4), also contributes to the active androgen pool in the prostate microenvironment, and while it has been shown to impact castration resistant prostate cancer, the C11-oxy C19 steroids together with the C11-oxy C21 steroids have not been studied in BPH. The study firstly investigated the metabolism of these adrenal steroids in the BPH-1 model. Comprehensive profiles identified 11keto-testosterone as the predominant active androgen in the metabolism of the C11-oxy C19 steroids, and we identified, for the first time, 11β-hydroxy-5α-androstane-3α,17β-diol, a novel steroid in the 11OHA4-pathway. Analysis of the inactivation and reactivation of the metabolites showed that DHT is more readily inactivated than 11keto-dihydrotestosterone (11KDHT). The conversion of 11β-hydroxyprogesterone (11βOHPROG) yielded 11keto-progesterone (11KPROG), while the latter yielded 11keto-dihydroprogesterone (11KDHPROG). BPH tissue analys...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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Authors: Nan LB, Yin XT, Gao JP Abstract BACKGROUND The aim of this study was to investigate the diagnostic value of (F/T)/PSAD for prostate cancer detection in the Chinese population. MATERIAL AND METHODS Data were collected retrospectively from patients with prostate cancer or benign prostatic hyperplasia from July 2009 to September 2014. SPSS 19.0 software was used for the receiver operating characteristic curve (ROC), and calculating sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV), respectively. Comparison of the area under ROC (AUC) was performed using the Me...
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Authors: Danilov SM, Kadrev AV, Kurilova OV, Tikhomirova VE, Kryukova OV, Mamedov VN, Kamalov DM, Danilova NV, Okhobotov DA, Gayfullin NM, Evdokimov VV, Alekseev BJ, Kost OA, Samokhodskaya LM, Kamalov AA Abstract Epithelial cells of prostate express significant level of ACE and, as a result, seminal fluid has 50-fold more ACE than plasma. The substitution of highly specialized prostate epithelial cells by tumor cells results in dramatic decrease in ACE production in prostate tissues. We performed detailed characterization of ACE status in prostate tissues from patients with benign prostate hyperplasia (BPH) and pro...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
AbstractMultiparametric MRI (mpMRI) of the prostate has evolved to be an integral component for the diagnosis, risk stratification, staging, and targeting of prostate cancer. However, anatomic and histologic mimics of prostate cancer on mpMRI exist. Anatomic feature that mimic prostate cancer on mpMRI include anterior fibromuscular stroma, normal central zone, periprostatic venous plexus, and thickened surgical capsule (transition zone pseudocapsule). Benign conditions such as post-biopsy hemorrhage, prostatitis or inflammation, focal prostate atrophy, benign prostatic hyperplasia nodules, and prostatic calcifications can ...
Source: Abdominal Imaging - Category: Radiology Source Type: research
Association between 5α-reductase inhibitors therapy and incidence, cancer-specific mortality, and progression of prostate cancer: evidence from a meta-analysis. Asian J Androl. 2019 Nov 08;: Authors: Luo LM, Yang RD, Wang JM, Zhao SK, Liu YZ, Zhu ZG, Xiang Q, Zhao ZG Abstract 5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression ...
Source: Asian Journal of Andrology - Category: Urology & Nephrology Authors: Tags: Asian J Androl Source Type: research
In conclusion, these results revealed that circZMIZ1 might serve as a novel biomarker and a treatment target for prostate cancer treatment. PMID: 31686520 [PubMed - as supplied by publisher]
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
Abstract PURPOSE: To investigate the clinical implications of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of patients prior to radical prostatectomy. MATERIALS AND METHODS: A total of 91 prostate cancer (PCa) patients and 50 benign prostatic hyperplasia (BPH) patients were enrolled from January 2016 to December 2017. The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of PCa and BPH patients were detected by flow cytometry, and the association of these T-cell populations with pathological Grade Group and pathological TNM classification was evaluated. Data ana...
Source: Urology Journal - Category: Urology & Nephrology Authors: Tags: Urol J Source Type: research
CONCLUSIONS: Although, the achieved results of this investigation demonstrated that the two examined genetic variants do not seem to be suitable markers for early diagnosis of prostate cancer in this pilot study; however increased risk for the disease is shown in GA heterozygotes and smokers which is indicative of some epigenetic factors influence on prostate cancer etiology. PMID: 31594215 [PubMed - as supplied by publisher]
Source: Human Antibodies - Category: Biochemistry Tags: Hum Antibodies Source Type: research
ConclusionsThe data shows promise of urine cell-free and vesicle cargo miRNA as prostate cancer biomarkers.Legal entity responsible for the studyThe authors.FundingThe study was supported by the Russian Science Foundation (no. 16-15-00124). Pavel P. Laktionov acknowledges financial support within the framework of the Russian state funded budget project # АААА-А17-117020210026-2 to the ICBFM SB RAS.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
To the Editor I would like to offer 2 points to expand on the important analysis by Sarkar and colleagues. First, use of a single prostate-specific antigen (PSA) multiplier for all men using 5 α-reductase inhibitors (5-ARIs) is probably not optimal. The goal is to estimate what each man’s PSA would have been in the absence of drug treatment. However, because 5-ARIs inhibit the common age-associated increase in gland volume and PSA, the PSA trajectory for a man being treated with a drug vs his counterfactual trajectory with no drug diverge over time. Furthermore, the benign prostatic hyperplasia component of tot...
Source: JAMA Internal Medicine - Category: Internal Medicine Source Type: research
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Source: Proteomics - Category: Biochemistry Authors: Tags: Research Article Source Type: research
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