Hormones and receptors coevolve to generate species diversity in hormone action. We compared the structure and function of androgen receptors (ARs) across fishes, with a focus on ARs in ghost knifefishes (Apteronotidae). Apteronotids, like many other teleosts, have two ARs (ARα and ARβ). ARβ is largely conserved, whereas ARα sequences vary considerably across species. The ARα ligand binding domain (LBD) has evolved under positive selection, and differences in the LBD across apteronotid species are associated with diversity in androgenic regulation of behavior. The Apteronotus leptorhynchus ARα LBD differs substantially from that of the Apteronotus albifrons ARα or the ancestral AR. Structural modeling and transactivation assays demonstrated that A. leptorhynchus ARα cannot bind androgens. We propose a model whereby relative expression of ARα versus ARβ in the brain, coupled with loss of androgen binding by ARα in A. leptorhynchus might explain reversals in androgenic regulation and sex differences in electrocommunication behavior.
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http://dx.doi.org/10.1016/j.mce.2023.112068 | DOI Listing |
Eur J Pharmacol
January 2025
School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address:
Pyruvate dehydrogenase kinase-1 (PDK1) plays a crucial role in cancer cell metabolism by regulating the glycolytic pathway. Although, inhibitors targeting PDK1 have been effective in inhibiting glycolysis in multiple cancers, their lack of selectivity leading to off-target effects limit their therapeutic benefit. Herein, we investigated the inhibitory potential of six PDK1 inhibitors on cellular proliferation, migration, and invasion of androgen-sensitive LNCaP and androgen-negative PC-3 prostate cancer cells.
View Article and Find Full Text PDFUnlabelled: Biomolecular condensates organize cellular environments and regulate key processes such as transcription. We previously showed that full-length androgen receptor (AR-FL), a major oncogenic driver in prostate cancer (PCa), forms nuclear condensates upon androgen stimulation in androgen-sensitive PCa cells. Disrupting these condensates impairs AR-FL transcriptional activity, highlighting their functional importance.
View Article and Find Full Text PDFEur 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 PDFInt J Mol Sci
January 2025
Division of Hematology/Oncology, University of Virginia, Charlottesville, VA 22903, USA.
Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.
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