Molecular insights into hormone regulation via signaling pathways in Sertoli cells: With discussion on infertility and testicular tumor

Ni, Fei-Da; Hao, Shuang-Li; Yang, Wan-Xi

doi:10.1016/j.gene.2020.144812

Cited by 25 publications

(10 citation statements)

References 145 publications

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“…The role of signaling pathways of the ER present in the membrane has been shown in many organs (reviewed by Levin, 2018) and also in Sertoli cells (reviewed by Lucas et al, 2014a;Meroni et al, 2019;Ni et al, 2020). The link between the activation of ER and protein kinases (ERK1/2 and AKT) has been shown in Sertoli cells from 15-day old rats (Lucas et al 2008(Lucas et al , 2014bRoyer et al, 2012) and from 20-day-old rats (present study).…”

Section: Discussionsupporting

confidence: 56%

The role of estrogen receptors in rat Sertoli cells at different stages of development

Macheroni

Lucas

Porto

2020

Heliyon

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The aim of the study was to investigate the effects of estrogen receptors (ESR1 and ESR2) on the expression of the proteins involved with proliferation (CCND1) and differentiation (CDKN1B and CTNNB) of Sertoli cells from rat in different stages of development. ESR1-selective agonist PPT, but not ESR2-selective agonist DPN, increased CCND1 expression in Sertoli cells from 5-and 15-day old rats. PPT did not have any effect on CCND1 expression in Sertoli cells from 20-and 30-day-old rats. DPN, but not PPT, increased CDKN1B expression in Sertoli cells from 15-, 20-, 30-day-old rats. DPN did not have any effect on Sertoli cells from 5-day-old rats. 17β-estradiol (E2) and PPT enhanced the [Methyl-3 H] thymidine incorporation in Sertoli cells from 15-day-old rats, whereas the treatment did not have any effect in 20-day-old rats. E2 and DPN, but not PPT, increased non-phosphorylated CTNNB expression in Sertoli cells from 20-day-old rats. This upregulation was blocked by ESR2-selective antagonist PHTPP. The activation of ESR1 and ESR2, respectively, plays a role in the proliferation and differentiation of Sertoli cells in a critical period of testicular development. Furthermore, in Sertoli cells from 20-dayold rats, upregulation of non-phosphorylated CTNNB by E2/ESR2, via c-SRC/ERK1/2 and PI3K/AKT, may play a role in the interaction between Sertoli cells and/or in cell-germ cell adhesion and/or in the stabilization and accumulation of CTNNB in the cytosol. CTNNB could be translocated to the nucleus and modulate the transcriptional activity of specific target genes. The present study reinforces the important role of estrogen in normal testis development.

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Section: Discussionsupporting

confidence: 56%

The role of estrogen receptors in rat Sertoli cells at different stages of development

Macheroni

Lucas

Porto

2020

Heliyon

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“…The findings that oestrogen can rapidly activate ERK1/2 to suppress SOX9 [161] demonstrates how essential assessing the effects of oestrogen on non-genomic targets is, as this type of signalling often establishes the changes required for genomic signalling to occur. Furthermore, these signalling pathways are critical for spermatogenesis and have been linked to male infertility [180], further supporting the impacts of exogenous oestrogen on non-genomic pathways and declining male reproductive health.…”

Section: Non-genomic Targets Of Oestrogen In the Gonadmentioning

confidence: 90%

Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health

Stewart

Mattiske

Pask

2020

IJMS

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The increasing incidence of testicular dysgenesis syndrome-related conditions and overall decline in human fertility has been linked to the prevalence of oestrogenic endocrine disrupting chemicals (EDCs) in the environment. Ectopic activation of oestrogen signalling by EDCs in the gonad can impact testis and ovary function and development. Oestrogen is the critical driver of ovarian differentiation in non-mammalian vertebrates, and in its absence a testis will form. In contrast, oestrogen is not required for mammalian ovarian differentiation, but it is essential for its maintenance, illustrating it is necessary for reinforcing ovarian fate. Interestingly, exposure of the bi-potential gonad to exogenous oestrogen can cause XY sex reversal in marsupials and this is mediated by the cytoplasmic retention of the testis-determining factor SOX9 (sex-determining region Y box transcription factor 9). Oestrogen can similarly suppress SOX9 and activate ovarian genes in both humans and mice, demonstrating it plays an essential role in all mammals in mediating gonad somatic cell fate. Here, we review the molecular control of gonad differentiation and explore the mechanisms through which exogenous oestrogen can influence somatic cell fate to disrupt gonad development and function. Understanding these mechanisms is essential for defining the effects of oestrogenic EDCs on the developing gonads and ultimately their impacts on human reproductive health.

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“…Complex cross-talks between signaling pathways and hormones, such as T3, have been described in several physiological models and in cancers (41,46,47). We reported here recent literature and also included new data on the intriguing relations between THs/TRa1 and WNT/b-catenin pathway in normal intestine and in tumors.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Hormone Nuclear Receptor TRα1 and Canonical WNT Pathway Cross-Regulation in Normal Intestine and Cancer

2021

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A pivotal role of thyroid hormones and their nuclear receptors in intestinal development and homeostasis have been described, whereas their involvement in intestinal carcinogenesis is still controversial. In this perspective article we briefly summarize the recent advances in this field and present new data regarding their functional interaction with one of the most important signaling pathway, such as WNT, regulating intestinal development and carcinogenesis. These complex interactions unveil new concepts and will surely be of importance for translational research.

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Molecular insights into hormone regulation via signaling pathways in Sertoli cells: With discussion on infertility and testicular tumor

Cited by 25 publications

References 145 publications

The role of estrogen receptors in rat Sertoli cells at different stages of development

The role of estrogen receptors in rat Sertoli cells at different stages of development

Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health

Thyroid Hormone Nuclear Receptor TRα1 and Canonical WNT Pathway Cross-Regulation in Normal Intestine and Cancer

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