Evolution of the androgen receptor: Perspectives from human health to dancing birds

Schuppe, Eric R.; Miles, Meredith C.; Fuxjager, Matthew J.

doi:10.1016/j.mce.2019.110577

Cited by 23 publications

(7 citation statements)

References 109 publications

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“…Focusing on only circulating hormones can lead to a binary understanding of these endocrine systems. As an example, we might conclude that sex differences in circulating levels of T have some functional importance across species, but this singular focus on T signal ignores the many other components of the androgen signaling system, including tissue sensitivity to the signal, and the rate of conversion to other hormones ( Rosvall, 2013 ; Lipshutz et al, 2019 ; Schuppe et al, 2020 ). Therefore, progress in our understanding of the hormonal phenotypic continuum must include a more comprehensive study of these endocrine axes, in both females and males.…”

Section: Where Do We Go From Here?mentioning

confidence: 99%

Beyond a biased binary: A perspective on the misconceptions, challenges, and implications of studying females in avian behavioral endocrinology

et al. 2022

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For decades, avian endocrinology has been informed by male perspectives and male-focused research, leaving significant gaps in our understanding of female birds. Male birds have been favored as research subjects because their reproductive behaviors are considered more conspicuous and their reproductive physiology is presumably less complex than female birds. However, female birds should not be ignored, as female reproductive behavior and physiology are essential for the propagation of all avian species. Endocrine research in female birds has made much progress in the last 20 years, but a substantial disparity in knowledge between male and female endocrinology persists. In this perspective piece, we provide examples of why ornithology has neglected female endocrinology, and we propose considerations for field and laboratory techniques to facilitate future studies. We highlight recent advances that showcase the importance of female avian endocrinology, and we challenge historic applications of an oversimplified, male-biased lens. We further provide examples of species for which avian behavior differs from the stereotypically described behaviors of male and female birds, warning investigators of the pitfalls in approaching endocrinology with a binary bias. We hope this piece will inspire investigators to engage in more comprehensive studies with female birds, to close the knowledge gap between the sexes, and to look beyond the binary when drawing conclusions about what is ‘male’ versus ‘female’ biology.

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Section: Where Do We Go From Here?mentioning

confidence: 99%

Beyond a biased binary: A perspective on the misconceptions, challenges, and implications of studying females in avian behavioral endocrinology

et al. 2022

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“…Mutation on the ARE site and/or the DBD could result in a disrupted signaling cascade ( 152 ). Therefore, the DBD remained practically unchanged for at least 500 million years ( 152 , 153 ). The mutations in humans compared to fishes in the DBD resulted in AR being able to bind to other hormone response elements as well as increasing transcriptional activity ( 154 ).…”

Section: Evolution and Phylogenetics Of The Polymorphic Repeat Regionsmentioning

confidence: 99%

The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease

Mészáros

Ahmed²,

Russo³

et al. 2022

Front. Med.

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Androgen receptor (AR) is a key member of nuclear hormone receptors with the longest intrinsically disordered N-terminal domain (NTD) in its protein family. There are four mono-amino acid repeats (polyQ1, polyQ2, polyG, and polyP) located within its NTD, of which two are polymorphic (polyQ1 and polyG). The length of both polymorphic repeats shows clinically important correlations with disease, especially with cancer and neurodegenerative diseases, as shorter and longer alleles exhibit significant differences in expression, activity and solubility. Importantly, AR has also been shown to undergo condensation in the nucleus by liquid-liquid phase separation, a process highly sensitive to protein solubility and concentration. Nonetheless, in prostate cancer cells, AR variants also partition into transcriptional condensates, which have been shown to alter the expression of target gene products. In this review, we summarize current knowledge on the link between AR repeat polymorphisms and cancer types, including mechanistic explanations and models comprising the relationship between condensate formation, polyQ1 length and transcriptional activity. Moreover, we outline the evolutionary paths of these recently evolved amino acid repeats across mammalian species, and discuss new research directions with potential breakthroughs and controversies in the literature.

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“…Once AR reaches the nuclear environment, it interacts with the AR response elements (AREs) that recruits it to the promoter region of the gene. Then, the AR transcriptional complex is completed by the addition of coregulators that can either promote gene activation or inhibition [35]. A brief scheme of such a mechanism is provided in Fig.…”

Section: Androgen Receptor (Ar) Signaling: An Overviewmentioning

confidence: 99%

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

et al. 2021

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Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.

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Evolution of the androgen receptor: Perspectives from human health to dancing birds

Cited by 23 publications

References 109 publications

Beyond a biased binary: A perspective on the misconceptions, challenges, and implications of studying females in avian behavioral endocrinology

Beyond a biased binary: A perspective on the misconceptions, challenges, and implications of studying females in avian behavioral endocrinology

The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

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