scholarly journals Androgen Receptor Plays a Vital Role in Benomyl- or Carbendazim-Induced Reproductive and Developmental Toxicity and Endocrine-Disrupting Activity in Rats

2018 ◽  
Author(s):  
Shui-Yuan Lu
Keyword(s):  
Androgen Receptor ◽  
Developmental Toxicity ◽  
Vital Role ◽  
Endocrine Disrupting

scholarly journals Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1169
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Surgical Therapy ◽  
Urothelial Cancer ◽  
Hormone Receptors ◽  
Estrogen Receptor Α ◽  
Vital Role ◽  
Sex Hormone ◽  
Sex Steroid Hormone

There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.

scholarly journals SAT-718 Inhibition of Androgen Receptor Activity by DDE Is Affected by Mutations in the BF3 Site

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andrea Lozano ◽  
Evangelia Kotsikorou ◽  
Frank B Dean
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Hek293 Cells ◽  
Luciferase Assay ◽  
Breakdown Product ◽  
Reporter System ◽  
Surface Binding ◽  
Endocrine Disrupting

Abstract The androgen receptor (AR) plays an important role in the development of the male phenotype and traits. Some diphenyl compounds inhibit AR activity by binding to a hydrophobic surface binding site, BF3. A similar diphenyl structure is found in 4,4’ DDT and its breakdown product 4,4’ DDE. Previous results showed that DDT and DDE induced the release of bound dihydrotestosterone from the AR ligand binding domain, with IC50 values ranging from 54 to 82uM. This suggested that DDT and related compounds may act as endocrine disrupting chemicals by binding to the BF3 site and inducing allosteric changes in the AR structure, disrupting binding of the steroid to the ligand binding domain. Here, an AR reporter system was transiently transfected into HEK293 cells and AR activity was measured using a dual luciferase assay. The system was used to measure the response of the AR protein to varying concentrations of dihydrotestosterone in the presence and absence of DDE. DDE inhibited the activation of AR by dihydrotestosterone under these conditions. Five mutant AR genes with amino acid changes in the BF3 site were tested for alterations in the ability of DDE to disrupt AR activity. The five mutations tested were F673K, F673W, G724R, G724M, and L830D. The ability of DDE to inhibit AR activity was reduced by the mutations in the BF3 site. These results suggest that DDE acts as an endocrine disrupting chemical (EDC) by binding to the BF3 site and allosterically regulating AR activity.

scholarly journals Nonmyocytic Androgen Receptor Regulates the Sexually Dimorphic Development of the Embryonic Bulbocavernosus Muscle

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2467-2479 ◽  
Author(s):  
Lerrie Ann Ipulan ◽  
Kentaro Suzuki ◽  
Yuki Sakamoto ◽  
Aki Murashima ◽  
Yuuki Imai ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Androgen Receptor ◽  
Cell Activation ◽  
Kinase Inhibitors ◽  
Myogenic Differentiation ◽  
Vital Role ◽  
Sexually Dimorphic ◽  
Receptor Knockout Mouse ◽  
Wild Type Female ◽  
Morphological Differences

The bulbocavernosus (BC) is a sexually dimorphic muscle observed only in males. Androgen receptor knockout mouse studies show the loss of BC formation. This suggests that androgen signaling plays a vital role in its development. Androgen has been known to induce muscle hypertrophy through satellite cell activation and myonuclei accretion during muscle regeneration and growth. Whether the same mechanism is present during embryonic development is not yet elucidated. To identify the mechanism of sexual dimorphism during BC development, the timing of morphological differences was first established. It was revealed that the BC was morphologically different between male and female mice at embryonic day (E) 16.5. Differences in the myogenic process were detected at E15.5. The male BC possesses a higher number of proliferating undifferentiated myoblasts. To identify the role of androgen signaling in this process, muscle-specific androgen receptor (AR) mutation was introduced, which resulted in no observable phenotypes. Hence, the expression of AR in the BC was examined and found that the AR did not colocalize with any muscle markers such as Myogenic differentiation 1, Myogenin, and paired box transcription factor 7. It was revealed that the mesenchyme surrounding the BC expressed AR and the BC started to express AR at E15.5. AR mutation on the nonmyocytic cells using spalt-like transcription factor 1 (Sall1) Cre driver mouse was performed, which resulted in defective BC formation. It was revealed that the number of proliferating undifferentiated myoblasts was reduced in the Sall1 Cre:ARL−/Y mutant embryos, and the adult mutants were devoid of BC. The transition of myoblasts from proliferation to differentiation is mediated by cyclin-dependent kinase inhibitors. An increased expression of p21 was observed in the BC myoblast of the Sall1 Cre:ARL−/Y mutant and wild-type female. Altogether this study suggests that the nonmyocytic AR may paracrinely regulate the proliferation of myoblast possibly through inhibiting p21 expression in myoblasts of the BC.

Developing a Laboratory Animal Model for Perinatal Endocrine Disruption: The Hamster Chronicles

2002 ◽  
Vol 227 (9) ◽  
pp. 709-723 ◽  
Author(s):  
William J. Hendry ◽  
Daniel M. Sheehan ◽  
Shafiq A. Khan ◽  
Jeffrey V. May
Keyword(s):  
Endocrine Disruption ◽  
Reproductive Tract ◽  
Developmental Toxicity ◽  
Endocrine Disrupting Chemicals ◽  
Experimental System ◽  
Endocrine Disrupting ◽  
Considerable Concern ◽  
Insight Into ◽  
Future Plans

At the biomedical, regulatory, and public level, considerable concern surrounds the concept that inappropriate exposure to endocrine-disrupting chemicals, especially during the prenatal and/or neonatal period, may disrupt normal reproductive tract development and adult function. The intent of this review was to 1. Describe some unique advantages of the hamster for perinatal endocrine disruptor (ED) studies, 2. Summarize the morphological and molecular consequences of exposure to the established perinatal ED, diethylstilbestrol, in the female and male hamster, 3. Present some new, histomorphological insight into the process of neonatal diethylstilbestrol-induced disruption in the hamster uterus, and 4. Introduce recent efforts and future plans to evaluate the potency and mechanism of action of other putative EDs in the hamster experimental system. Taken together, the findings indicate that the hamster represents a unique and sensitive in vivo system to probe the phenomenon of endocrine disruption. The spectrum of candidate endpoints includes developmental toxicity, neoplasia, and more subtle endpoints of reproductive dysfunction.

scholarly journals In Vitro Characterization of the Endocrine Disrupting Effects of Per- and Poly-fluoroalkyl Substances (PFASs) on the Human Androgen Receptor

2022 ◽  
pp. 128243
Author(s):  
Phum Tachachartvanich ◽  
Azhagiya Singam Ettayapuram Ramaprasad ◽  
Kathleen A. Durkin ◽  
J. David Furlow ◽  
Martyn T. Smith ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
In Vitro Characterization ◽  
Endocrine Disrupting ◽  
Human Androgen Receptor

scholarly journals Developmental exposure to the DE-71 mixture of polybrominated diphenyl ether (PBDE) flame retardants induce a complex pattern of endocrine disrupting effects in rats

PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12738
Author(s):  
Louise Ramhøj ◽  
Karen Mandrup ◽  
Ulla Hass ◽  
Terje Svingen ◽  
Marta Axelstad
Keyword(s):  
Mammary Gland ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Developmental Stages ◽  
Developmental Toxicity ◽  
Diphenyl Ether ◽  
Male Offspring ◽  
Developmental Exposure ◽  
Endocrine Disrupting

Polybrominated diphenyl ethers (PBDEs) are legacy compounds with continued widespread human exposure. Despite this, developmental toxicity studies of DE-71, a mixture of PBDEs, are scarce and its potential for endocrine disrupting effects in vivo is not well covered. To address this knowledge gap, we carried out a developmental exposure study with DE-71. Pregnant Wistar rat dams were exposed to 0, 40 or 60 mg/kg bodyweight/day from gestation day 7 to postnatal day 16, and both sexes were examined. Developmental exposure affected a range of reproductive toxicity endpoints. Effects were seen for both male and female anogenital distances (AGD), with exposed offspring of either sex displaying around 10% shorter AGD compared to controls. Both absolute and relative prostate weights were markedly reduced in exposed male offspring, with about 40% relative to controls. DE-71 reduced mammary gland outgrowth, especially in male offspring. These developmental in vivo effects suggest a complex effect pattern involving anti-androgenic, anti-estrogenic and maybe estrogenic mechanisms depending on tissues and developmental stages. Irrespective of the specific underlying mechanisms, these in vivo results corroborate that DE-71 causes endocrine disrupting effects and raises concern for the effects of PBDE-exposure on human reproductive health, including any potential long-term consequences of disrupted mammary gland development.

Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

2012 ◽  
Vol 34 (2) ◽  
pp. 237-250 ◽  
Author(s):  
Pernille Rosenskjold Jacobsen ◽  
Marta Axelstad ◽  
Julie Boberg ◽  
Louise Krag Isling ◽  
Sofie Christiansen ◽  
...  
Keyword(s):  
Low Dose ◽  
Developmental Toxicity ◽  
Rat Offspring ◽  
Endocrine Disrupting
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