Zebrafish Nedd8 Facilitates Ovarian Development and the Maintenance of Female Secondary Sexual Characteristics Via Suppression of Androgen Receptor Activity

2019 ◽  
Author(s):  
Guangqin Yu ◽  
Xing Liu ◽  
Dawei Zhang ◽  
Jing Wang ◽  
Gang Ouyang ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Ovarian Development ◽  
Receptor Activity ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
Androgen Receptor Activity ◽  
Secondary Sexual

scholarly journals Zebrafish Nedd8 facilitates ovarian development and the maintenance of female secondary sexual characteristics via suppression of androgen receptor activity

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev194886 ◽  
Author(s):  
Guangqing Yu ◽  
Xing Liu ◽  
Dawei Zhang ◽  
Jing Wang ◽  
Gang Ouyang ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Protein Activity ◽  
Secondary Sexual Characteristics ◽  
Pectoral Fins ◽  
Sexual Characteristics ◽  
Androgen Receptor Activity ◽  
Regulate Protein ◽  
Female Zebrafish ◽  
Secondary Sexual

ABSTRACTNedd8 is a ubiquitin-like protein that covalently conjugates to target proteins through neddylation. In addition to cullin-RING ligases, neddylation also modifies non-cullin proteins to regulate protein activity, stability and localization. However, the roles of NEDD8 remain largely unknown in vivo. Here, we found that loss of nedd8 in female zebrafish led to defects in oogenesis, disrupted oocyte maturation and stimulated growth of the breeding tubercles (BTs) on the pectoral fins. The BTs are normally present in males, not females. However, the loss of one copy of ar can partially rescue the phenotypes displayed by nedd8-null female zebrafish. Further assays indicated that Nedd8 conjugates to Ar and Ar is neddylated at lysine 475 and lysine 862. Moreover, Nedd8 conjugation efficiently suppressed Ar transcriptional activity. Lysine 862 (K862) of Ar is the key site modified by neddylation to modulate Ar transcriptional activity. Thus, our results not only demonstrated that Nedd8 modulates ovarian maturation and the maintenance of female secondary sexual characteristics of female zebrafish in vivo, but also indicated that androgen signaling is strictly regulated by nedd8.

scholarly journals A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erik Bovinder Ylitalo ◽  
Elin Thysell ◽  
Mattias Landfors ◽  
Maria Brattsand ◽  
Emma Jernberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Bone Metastases ◽  
Metastatic Prostate Cancer ◽  
Tumor Biology ◽  
Receptor Activity ◽  
Mrna Levels ◽  
Androgen Receptor Activity ◽  
Patient Prognosis

Abstract Background Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity. Materials and methods Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity. Results Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT. Conclusions A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells

2012 ◽  
Vol 22 (17) ◽  
pp. 5470-5474 ◽  
Author(s):  
Byung Jun Ryu ◽  
Seung-hwa Baek ◽  
Jiyeon Kim ◽  
Su Jung Bae ◽  
Sung-Youn Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Receptor Activity ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Lncap Cells ◽  
Androgen Receptor Activity ◽  
Ck2 Inhibitor

Comparative urogenital morphology and external sex determination in muskellunge, Esox masquinongy Mitchill

1989 ◽  
Vol 67 (4) ◽  
pp. 1053-1060 ◽  
Author(s):  
Bernard Lebeau ◽  
Gérard Pageau
Keyword(s):  
Ventral Surface ◽  
Northern Pike ◽  
Structural Basis ◽  
Simple Method ◽  
Esox Masquinongy ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
Spawning Behaviour ◽  
Accurate Indicator ◽  
Secondary Sexual

Primary and secondary sexual characteristics in northern pike, Esox lucius Linneaus, and muskellunge, Esox masquinongy Mitchill, differ markedly. Differences in the internal urogenital anatomy include the structure of the genital ducts and the angle they form with the ventral surface. Externally, the genital and urinary ducts open directly to the environment in northern pike, whereas in muskellunge they open into a muscular papilla and then through a urogenital pore. Differences in sexual dimorphism between the two closely related esocids constitute a structural basis to explain the known differences in spawning behaviour and reproductive success. Differences in secondary sexual characteristics explain why the methods developed by Demchenko or Casselman to externally sex pike are inapplicable to muskellunge. To develop and test two external sexing techniques for muskellunge, specimens were collected from two regions in Canada from 1980 to 1987. Examination of reproductive products obtained from stripping provided an accurate indicator of sex and sexual maturity, but demonstrated serious limitations. A simple method to sex muskellunge by examination of the external urogenital morphology is described for juveniles and adults. Dissection of fish revealed that with the urogenital examination technique we sexed juveniles with a success rate of 92–98%, and adults with 100% accuracy.

scholarly journals The Deubiquitinating Enzyme USP7 Regulates Androgen Receptor Activity by Modulating Its Binding to Chromatin

2015 ◽  
Vol 290 (35) ◽  
pp. 21713-21723 ◽  
Author(s):  
Shu-Ting Chen ◽  
Maiko Okada ◽  
Ryuichiro Nakato ◽  
Kosuke Izumi ◽  
Masashige Bando ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Activity ◽  
Deubiquitinating Enzyme ◽  
Androgen Receptor Activity

The effects of phthalate and nonylphenol exposure on body size and secondary sexual characteristics during puberty

2015 ◽  
Vol 218 (7) ◽  
pp. 603-615 ◽  
Author(s):  
Jia-Woei Hou ◽  
Ching-Ling Lin ◽  
Yen-An Tsai ◽  
Chia-Huang Chang ◽  
Kai-Wei Liao ◽  
...  
Keyword(s):  
Body Size ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
Secondary Sexual
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