Epitestosterone is a stereoisomer of the active androgen testosterone and its circulating concentrations are similar to those of testosterone in women and children. However, its biological function and pathways of metabolism remain unknown. The structural similarity to testosterone suggests a potential function in the modulation of androgen receptor signalling. It is well established that the conversion of testosterone to 5α-dihydrotestosterone enhances local androgen receptor signalling. In this study, we show that epitestosterone is metabolized to 5α-dihydroepitestosterone by both human steroid 5α-reductase isoforms, SRD5A1 and SRD5A2. Using two different variations of a reporter assay for transactivation of the human androgen receptor, we show that epitestosterone is a partial AR agonist and that the 5α-reduction of epitestosterone increases its androgenic activity. In line with this, we show that 5α-reduction of epitestosterone reduces its ability to antagonize 5α-dihydrotestosterone-induced androgen receptor transactivation. In conclusion, we provide evidence that steroid 5α-reductases regulate the modulatory effect of epitestosterone on androgen receptor signalling.
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http://dx.doi.org/10.1016/j.jsbmb.2024.106516 | DOI Listing |
Eur J Pharmacol
January 2025
Department of Urology, Brown Cancer Center, 505 S Hancock Street, Louisville, KY, USA. Electronic address:
Manzamine A, a natural compound derived from various sponge genera, features a β-carboline structure and exhibits a range of biological activities, including anti-inflammatory and antimalarial effects. Its potential as an anticancer agent has been explored in several tumor models, both in vitro and in vivo, showing effects through mechanisms such as cytotoxicity, regulation of the cell cycle, inhibition of cell migration, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis through multi-target interactions of E2F transcriptional factors, ribosomal S6 kinases, androgen receptor (AR), SIX1, GSK-3β, V-ATPase, and p53/p21/p27 cascades. This systematic review evaluates existing literature on the potential application of this marine alkaloid as a novel cancer therapy, highlighting its promising ability to inhibit cancer cell growth while causing minimal side effects.
View Article and Find Full Text PDFChemosphere
January 2025
Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto de Investigaciones en Ciencias de La Salud (INICSA), Córdoba, Argentina; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica. Córdoba, Argentina. Electronic address:
DEHP is a prevalent phthalate with wide industrial applications and well-documented endocrine-disrupting effects, including the potential disruption of AR signaling in different tissues. The present study aimed to investigate the effects of gestational and lactational exposure to environmentally relevant DEHP concentrations on AR expression and subcellular localization in the pituitary gland, the master endocrine organ, with a focus on gonadotroph cells by in vivo and in vitro approaches. After DEHP exposure during gestation and lactation, a sex-specific modulation was detected in AR-positive pituitary cells and AR protein expression as assessed through flow cytometry and western blot.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Cytobiology and Proteomics, Medical University of Lodz, 92-215 Lodz, Poland.
Background: Androgenic anabolic steroids (AASs) are synthetic drugs structurally related to testosterone, with the ability to bind to androgen receptors. Their uncontrolled use by professional and recreational sportspeople is a widespread problem. AAS abuse is correlated with severe damage to the cardiovascular system, including changes in homeostasis and coagulation disorders.
View Article and Find Full Text PDFNutrients
January 2025
Epidemiology Unit, Istituto Dermopatico dell'Immacolata (IDI-IRCCS-FLMM), 00167 Rome, Italy.
Unlabelled: Single nucleotide polymorphisms (SNPs) found to be associated with Androgenetic Alopecia (AGA) to date, are characterized by an apparent reduced penetrance into the phenotype suggesting a role of other factors in the etiology of AGA.
Objective: We conducted a study to investigate the role of specific allelic variants in AGA controlling for nutritional and lifestyle factors.
Methods: Individual patterns of SNPs present in the baldness susceptibility locus at 20p11 (rs1160312 and rs6113491) or close to the androgen receptor (AR) gene in chromosome X (rs1041668) were investigated in 212 male subjects.
Int J Mol Sci
January 2025
National Cancer Institute, P. Baublio Str. 3B, LT-08406 Vilnius, Lithuania.
This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers-Prostate-Specific Membrane Antigen (), Prostate Cancer Antigen 3 (), and androgen receptor () genes-for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers.
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