Androgens modulate gene expression and specific DNA methylation pattern of steroid 5α-reductases in the frog Silurana tropicalis

Bissegger, Sonja; Langlois, Valérie S.

doi:10.1016/j.ygcen.2016.03.021

Cited by 12 publications

(11 citation statements)

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“…Exposure to 5α-DHT did not modulate srd5α2 transcript levels in testes. Bissegger and Langlois (2016) previously confirmed that srd5a2 expression was unaffected by exposure to T, 5α-DHT, or 5β-DHT ex vivo in testis tissue of frogs. However, cyp19 transcripts in-and E 2 production from-whole testis significantly increased following exposure to 5α-DHT.…”

Section: Discussionsupporting

confidence: 58%

“…Exposure to T3 has been shown to affect histone and polymerase II modification, but does not affect hyper-methylation in the promoter region of trβ in X. laevis tadpoles (Kasai et al, 2015). Moreover, sexually dimorphic DNA methylation patterning has been observed in sex steroid-related genes in frogs and fish (Bissegger and Langlois, 2016;Navarro-Martín et al, 2011;Contractor et al, 2004), but sex differences in methylation patterns have not yet been investigated with regard to TH-related genes. Tissue and age specific DNA methylation and histone modification patterns have however been thoroughly studied in amphibians.…”

Section: Discussionmentioning

confidence: 99%

“…The individual treatments occupied a total of eight wells or two columns with the whole testes assay spanning two 24-well plates (32 wells total) and ovary pieces assay spanning two 24-well plates (32 wells total). These concentrations were chosen based on an ex vivo study conducted with S. tropicalis (Bissegger and Langlois, 2016). The 24-well plates were incubated for 6 h at 26°C using an orbital shaker.…”

Section: Animals and Exposurementioning

confidence: 99%

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Thyroid hormones and androgens differentially regulate gene expression in testes and ovaries of sexually mature Silurana tropicalis

Campbell

Langlois

2018

General and Comparative Endocrinology

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A series of ex vivo exposures using testicular and ovarian tissues of sexually mature Western clawed frogs (Silurana tropicalis) were designed to examine molecular mechanisms of thyroid hormone (TH) and androgen crosstalk sans hypophyseal feedback as well as investigate potential sex-specific differences. Tissues were exposed ex vivo to either triiodothyronine (T3), iopanoic acid (IOP), one co-treatment of IOP + 5α-dihydrotestosterone (5α-DHT), 5α-DHT, 5β-dihydrotestosterone (5β-DHT), or testosterone (T). Direct exposure to different androgens led to androgen specific increases in thyroid receptor and deiodinase transcripts in testes (trβ and dio1) but a decrease in expression in ovaries (trβ and dio3), suggesting that male and female frogs can be differently affected by androgenic compounds. Moreover, exposure to select androgens differentially increased estrogen-related transcription (estrogen receptor alpha (erα) and aromatase (cyp19)) and production (estradiol) in ovaries and testes indicating the activation of alternate metabolic pathways yielding estrogenic metabolites. Sex-steroid-related transcription (i.e., steroid 5α-reductase type 2 (srd5α2) and erα) and production (i.e., 5α-DHT) were also differentially regulated by THs. The presence and frequency of transcription factor binding sites in the putative promoter regions of TH- and sex steroid-related genes were also examined in S. tropicalis, rodent, and fish models using in silico analysis. In summary, this study provides an improved mechanistic understanding of TH- and androgen-mediated actions and reveals differential transcriptional effects as a function of sex in frogs.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Exposurementioning

confidence: 99%

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Thyroid hormones and androgens differentially regulate gene expression in testes and ovaries of sexually mature Silurana tropicalis

Campbell

Langlois

2018

General and Comparative Endocrinology

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“…Plasma levels of E 2 were found to be unaffected by in vivo exposure to 5α-DHT in male and female adult frogs (X. laevis : Urbatzka et al, 2007;Coady et al, 2005); however, embryos lack hypophyseal-feedback mechanisms which could explain why expression differs. Moreover, Bissegger and Langlois (2016) demonstrated that androgens (T, 5α-DHT, and 5β-DHT) significantly decreased srd5α1 and srd5α3 transcripts in S. tropicalis ovary tissue ex vivo. Exposure to the potent androgen, 5α-DHT also modulated TH related gene expression in embryonic S. tropicalis.…”

Section: Discussionmentioning

confidence: 92%

Expression of sf1 and dax-1 are regulated by thyroid hormones and androgens during Silurana tropicalis early development

Campbell

Langlois

2018

General and Comparative Endocrinology

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Thyroid hormones (THs) and androgens have been shown to be extensively involved in sexual development; however, relatively little is known with regard to TH-related and androgenic actions in sex determination. We first established expression profiles of three sex-determining genes (sf1, dax-1, and sox9) during the embryonic development of Western clawed frogs (Silurana tropicalis). Transcripts of sf1 and sox9 were detected in embryos before the period in which embryonic transcription commences indicating maternal transfer, whereas dax-1 transcripts were not detected until later in development. To examine whether TH status affects sex-determining gene expression in embryonic S. tropicalis, embryos were exposed to co-treatments of iopanoic acid (IOP), thyroxine (T4), or triiodothyronine (T3) for 96 h. Expression profiles of TH receptors and deiodinases reflect inhibition of peripheral deiodinase activity by IOP and recovery by T3. Relevantly, elevated TH levels significantly increased the expression of sf1 and dax-1 in embryonic S. tropicalis. Further supporting TH-mediated regulation, examination of the presence and frequency of transcription factor binding sites in the putative promoter regions of sex-determining genes in S. tropicalis and rodent and fish models using in silico analysis also identified TH motifs in the putative promoter regions of sf1 and dax-1. Together these findings advocate that TH actions as early as the period of embryogenesis may affect gonadal fate in frogs. Mechanisms of TH and androgenic crosstalk in relation to the regulation of steroid-related gene expression were also investigated.

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“…DNA methylation inhibits the bind between transcriptional factors and their target sequences, both promoters, and introns, impeding the activation of transcriptional expression. In an animal model, 5α-DHT increased DNA methylation of srd5α2 (steroid 5α-reductases type 2) [ 36 ]. The latter is also regulated by chromatin condensation degree [ 37 ].…”

Section: From Aas Genotoxicity To Carcinogenicitymentioning

confidence: 99%

Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review

et al. 2018

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Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor.AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via IGF-1. This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation.AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage.

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Androgens modulate gene expression and specific DNA methylation pattern of steroid 5α-reductases in the frog Silurana tropicalis

Cited by 12 publications

References 54 publications

Thyroid hormones and androgens differentially regulate gene expression in testes and ovaries of sexually mature Silurana tropicalis

Thyroid hormones and androgens differentially regulate gene expression in testes and ovaries of sexually mature Silurana tropicalis

Expression of sf1 and dax-1 are regulated by thyroid hormones and androgens during Silurana tropicalis early development

Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review

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