The meaning of non-classical estrogen receptors and peroxisome proliferator-activated receptor for boar Leydig cell of immature testis

Kotula–Balak, Małgorzata; Duliban, Michał; Pawlicki, Piotr; Tuz, R.; Bilińska, Barbara; Płachno, Bartosz J.; Arent, Zbigniew; Krakowska, I.; Tarasiuk, K.

doi:10.1016/j.acthis.2020.151526

Cited by 9 publications

(11 citation statements)

References 86 publications

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“…Testicular tissues were cut into 4-µm-thin sections. For antigen retrieval, endogenous peroxidase neutralization and blocking of non-specific binding sites were performed as described previously [80]. Thereafter, the sections were incubated overnight at 4 no.…”

Section: Immunohistochemistrymentioning

confidence: 99%

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Witkowski

Pardyak

Pawlicki

et al. 2021

IJMS

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Cryptorchidism in horses is a commonly occurring malformation. The molecular basis of this pathology is not fully known. In addition, the origins of high intratesticular estrogen levels in horses remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor (GPER) and establish histological and biochemical cryptorchid testis status, healthy and cryptorchid horse testes were subjected to scanning electron microscopy analysis, histochemical staining for total protein (with naphthol blue black; NBB), acid content (with toluidine blue O; TBO), and polysaccharide content (with periodic acid–Schiff; PAS). The expression of GPER was analyzed by immunohistochemistry and Western blot. GPER-mediated intracellular cAMP and calcium (Ca2+) signaling were measured immunoenzymatically or colorimetrically. Our data revealed changes in the distribution of polysaccharide content but not the protein and acid content in the cryptorchid testis. Polysaccharides seemed to be partially translocated from the interstitial compartment to the seminiferous tubule compartment. Moreover, the markedly decreased expression of GPER and GPER downstream molecules, cAMP and Ca2+, suggests their potential role in testis pathology. Increased estrogen levels in cryptorchid conditions may be linked to disturbed GPER signaling. We postulate that GPER is a prominent key player in testis development and function and may be used as a new biomarker of horse testis in health and disease.

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Section: Immunohistochemistrymentioning

confidence: 99%

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Witkowski

Pardyak

Pawlicki

et al. 2021

IJMS

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“…Several recent studies revealed GPER presence and its implication in the testes functions of various animals [25,26,27,28]. Moreover, the association of GPER and estrogen-related receptors or PPAR interaction in the control of healthy and tumor testicular cells in rodents and humans was previously demonstrated by us [29,30,6,31]. Nowadays, the GPER antagonist is monitored as a potential therapeutic drug for male infertility treatment [32].…”

Section: Introductionmentioning

confidence: 93%

“…The global gene expression analysis of differentially regulated transcripts was followed by a cluster analysis and a pathway analysis, respectively. This included an analysis of differentially regulated genes and proteins expressed in testes with a known morphological status that were partially earlier studied by us [29,30,33,6,28,31]. To the best of the authors' knowledge, no research has engaged in this type of approach before.…”

Section: Introductionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ, but Not α or G-Protein Coupled Estrogen Receptor Drives Functioning of Postnatal Boar Testis—Next Generation Sequencing Analysis

Duliban

Pawlicki

Gurgul

et al. 2021

Animals

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Porcine tissue gene expression is highly similar to the expression of homologous genes in humans. Based on this fact, the studies on porcine tissues can be employed to understand human physiology and to predict or treat diseases. Our prior studies clearly showed that there was a regulatory partnership of the peroxisome proliferator-activated receptor (PPAR) and the G-protein coupled membrane estrogen receptor (GPER) that relied upon the tumorigenesis of human and mouse testicular interstitial cells, as well as the PPAR-estrogen related receptor and GPER–xenoestrogen relationships which affected the functional status of immature boar testes. The main objective of this study was to identify the biological processes and signaling pathways governed by PPARα, PPARγ and GPER in the immature testes of seven-day-old boars after pharmacological receptor ligand treatment. Boar testicular tissues were cultured in an organotypic system with the respective PPARα, PPARγ or GPER antagonists. To evaluate the effect of the individual receptor deprivation in testicular tissue on global gene expression, Next Generation Sequencing was performed. Bioinformatic analysis revealed 382 transcripts with altered expression. While tissues treated with PPARα or GPER antagonists showed little significance in the enrichment analysis, the antagonists challenged with the PPARγ antagonist displayed significant alterations in biological processes such as: drug metabolism, adhesion and tubule development. Diverse disruption in the Notch signaling pathway was also observed. The findings of our study proposed that neither PPARα nor GPER, but PPARγ alone seemed to be the main player in the regulation of boar testes functioning during early the postnatal developmental window.

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“…This last aspect will be explained in the paragraph on GPER role in testicular tumors. A very recent study by Kotula-Balak and colleagues [46] asserted that exists a GPER-ERRβ-PPARγ interaction in the immature wild boar testicle that affects Leydig cells function [46]. It also highlights the involvement of these receptors in cellular processes through cAMP activation and Raf/Ras/ERK pathways modulating cholesterol concentration and estradiol levels.…”

Section: Gper In Leydig Cellsmentioning

confidence: 99%

“…Testicular Physiology Testicular Tumors SPG GPER activation induces proliferation [84][85][86] GPER is overexpressed in seminoma and embryonal carcinoma [119], (whereas ERα is missing [120]) GPER mediates estrogen and xenoestrogen-dependent proliferation in seminomas [123][124][125]128,129] SPT GPER activation induces apoptosis [31,32,88] RS GPER activation induces apoptosis [30] LC GPER is involved in: LC morphology and function [38] LCT [where ERα is overexpressed]: GPER activation decrease cell proliferation and induces apoptosis [130] Xenoestrogens decrease GPER expression favoring LCT progression [133] GPER is involved in LCT control of lipid metabolism and steroidogenesis (interaction with PPAR) [134] LC androgens production [40] LC lipophagy inhibition [43] LC miRNA biogenesis [49] LC development and function [PPAR crosstalk] [46] SC GPER activation induces proliferation in immature testis [65][66][67][68] Sertoli cell tumors: GPER is expressed but the role has been not identified. In interstitial compartment, GPER appears to play an important role in regulating estrogen-dependent lipid homeostasis and testosterone biosynthesis that occur in Leydig cells.…”

Section: Cell Typesmentioning

confidence: 99%

Role of GPER-Mediated Signaling in Testicular Functions and Tumorigenesis

Chimento

Luca

Nocito

et al. 2020

Cells

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Estrogen signaling plays important roles in testicular functions and tumorigenesis. Fifteen years ago, it was discovered that a member of the G protein-coupled receptor family, GPR30, which binds also with high affinity to estradiol and is responsible, in part, for the rapid non-genomic actions of estrogens. GPR30, renamed as GPER, was detected in several tissues including germ cells (spermatogonia, spermatocytes, spermatids) and somatic cells (Sertoli and Leydig cells). In our previous review published in 2014, we summarized studies that evidenced a role of GPER signaling in mediating estrogen action during spermatogenesis and testis development. In addition, we evidenced that GPER seems to be involved in modulating estrogen-dependent testicular cancer cell growth; however, the effects on cell survival and proliferation depend on specific cell type. In this review, we update the knowledge obtained in the last years on GPER roles in regulating physiological functions of testicular cells and its involvement in neoplastic transformation of both germ and somatic cells. In particular, we will focus our attention on crosstalk among GPER signaling, classical estrogen receptors and other nuclear receptors involved in testis physiology regulation.

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The meaning of non-classical estrogen receptors and peroxisome proliferator-activated receptor for boar Leydig cell of immature testis

Cited by 9 publications

References 86 publications

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Peroxisome Proliferator-Activated Receptor γ, but Not α or G-Protein Coupled Estrogen Receptor Drives Functioning of Postnatal Boar Testis—Next Generation Sequencing Analysis

Role of GPER-Mediated Signaling in Testicular Functions and Tumorigenesis

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