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      Expression of novel androgen receptors in three GnRH neuron subtypes in the cichlid brain

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      research-article
      a , * , a , b , *
      bioRxiv
      Cold Spring Harbor Laboratory
      Androgen receptors, paralogs, genome duplication, GnRH, A. burtoni

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          Abstract

          Within a social hierarchy, an individuals’ social status determines its physiology and behavior. In A. burtoni, subordinate males can rise in rank to become dominant, which is accompanied by the upregulation of the entire HPG axis, including activation of GnRH1 neurons, a rise in circulating androgen levels and the display of specific aggressive and reproductive behaviors. Cichlids possess two other GnRH subtypes, GnRH2 and GnRH3, the latter being implicated in the display of male specific behaviors. Interestingly, some studies showed that these GnRH neurons are responsive to fluctuations in circulating androgen levels, suggesting a link between GnRH neurons and androgen receptors (ARs). Due to a teleost-specific whole genome duplication, A. burtoni possess two AR paralogs (ARα and ARβ) that are encoded by two different genes, ar1 and ar2, respectively. Even though social status has been strongly linked to androgens, whether ARα and/or ARβ are present in GnRH neurons remains unclear. Here, we used immunohistochemistry and in situ hybridization chain reaction (HCR) to investigate ar1 and ar2 expression specifically in GnRH neurons. We find that all GnRH1 neurons intensely express ar1 but only a few of them express ar2, suggesting the presence of genetically-distinct GnRH1 subtypes. Very few ar1 and ar2 transcripts were found in GnRH2 neurons. GnRH3 neurons were found to express both ar genes. The presence of distinct ar genes within GnRH neuron subtypes, most clearly observed for GnRH1 neurons, suggests differential control of these neurons by androgenic signaling. These findings provide valuable insight for future studies aimed at disentangling the androgenic control of GnRH neuron plasticity and reproductive plasticity across teleosts.

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          Most cited references55

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          Whole-genome duplication in teleost fishes and its evolutionary consequences.

          Whole-genome duplication (WGD) events have shaped the history of many evolutionary lineages. One such duplication has been implicated in the evolution of teleost fishes, by far the most species-rich vertebrate clade. After initial controversy, there is now solid evidence that such event took place in the common ancestor of all extant teleosts. It is termed teleost-specific (TS) WGD. After WGD, duplicate genes have different fates. The most likely outcome is non-functionalization of one duplicate gene due to the lack of selective constraint on preserving both. Mechanisms that act on preservation of duplicates are subfunctionalization (partitioning of ancestral gene functions on the duplicates), neofunctionalization (assigning a novel function to one of the duplicates) and dosage selection (preserving genes to maintain dosage balance between interconnected components). Since the frequency of these mechanisms is influenced by the genes' properties, there are over-retained classes of genes, such as highly expressed ones and genes involved in neural function. The consequences of the TS-WGD, especially its impact on the massive radiation of teleosts, have been matter of controversial debate. It is evident that gene duplications are crucial for generating complexity and that WGDs provide large amounts of raw material for evolutionary adaptation and innovation. However, it is less clear whether the TS-WGD is directly linked to the evolutionary success of teleosts and their radiation. Recent studies let us conclude that TS-WGD has been important in generating teleost complexity, but that more recent ecological adaptations only marginally related to TS-WGD might have even contributed more to diversification. It is likely, however, that TS-WGD provided teleosts with diversification potential that can become effective much later, such as during phases of environmental change.
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            The influence of social hierarchy on primate health.

            Dominance hierarchies occur in numerous social species, and rank within them can greatly influence the quality of life of an animal. In this review, I consider how rank can also influence physiology and health. I first consider whether it is high- or low-ranking animals that are most stressed in a dominance hierarchy; this turns out to vary as a function of the social organization in different species and populations. I then review how the stressful characteristics of social rank have adverse adrenocortical, cardiovascular, reproductive, immunological, and neurobiological consequences. Finally, I consider how these findings apply to the human realm of health, disease, and socioeconomic status.
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              The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis

              Master transcription factors interact with DNA to establish cell-type identity and to regulate gene expression in mammalian cells 1,2 . The genome-wide map of these transcription factor binding sites has been termed the cistrome 3 . Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13, co-localized with the reprogrammed AR sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium towards transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.

                Author and article information

                Contributors
                Role: conceptualizationRole: investigationRole: data curationRole: validationRole: visualizationRole: writing - original draftRole: writing - review and editing
                Role: conceptualizationRole: funding acquisitionRole: resourcesRole: supervisionRole: writing - review and editing
                Journal
                bioRxiv
                BIORXIV
                bioRxiv
                Cold Spring Harbor Laboratory
                04 February 2024
                : 2024.02.02.578641
                Affiliations
                [a ]University of Houston, Department of Psychology, United States of America
                [b ]University of Houston, Department of Biology and Biochemistry, United States of America
                Author notes
                Author information
                http://orcid.org/0000-0002-1903-883X
                http://orcid.org/0000-0002-1403-5277
                Article
                10.1101/2024.02.02.578641
                10862814
                38352335
                a6d483fb-31cd-4f44-9b94-23178b6c9ea6

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.

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                androgen receptors,paralogs,genome duplication,gnrh,a. burtoni

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