Targeting human glutathione transferase A3-3 attenuates progesterone production in human steroidogenic cells

Raffalli-Mathieu, Françoise; Orre, Carolina; Stridsberg, Mats; Edalat, Maryam; Mannervik, Bengt

doi:10.1042/bj20080397

Cited by 24 publications

(25 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PGR has been described before, but no difference between pregnant and non-pregnant could be confirmed with quantitative PCR [28]. GSTA3 that was present in some of the pregnancy models also has a link with progesterone production [24] reiterating the importance of the steroidogenesis pathway. The function of EFNB2 in the ovary is not yet known, but B-class ephrins were proposed to be related to the luteinization process [19] and the ephrin B2 receptor was found differently expressed between CC from normal oocytes compared to aneuploid oocytes [9].…”

Section: Discussionmentioning

confidence: 87%

Pregnancy Prediction in Single Embryo Transfer Cycles after ICSI Using QPCR: Validation in Oocytes from the Same Cohort

Wathlet¹,

Adriaenssens²,

Segers³

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Cumulus cell (CC) gene expression is being explored as an additional method to morphological scoring to choose the embryo with the highest chance to pregnancy. In 47 ICSI patients with single embryo transfer (SET), from which individual CC samples had been stored, 12 genes using QPCR were retrospectively analyzed. The CC samples were at the same occasion also used to validate a previously obtained pregnancy prediction model comprising three genes (ephrin-B2 (EFNB2), calcium/calmodulin-dependent protein kinase ID, stanniocalcin 1). Latter validation yielded a correct pregnant/non-pregnant classification in 72% of the samples. Subsequently, 9 new genes were analyzed on the same samples and new prediction models were built. Out of the 12 genes analyzed a combination of the best predictive genes was obtained by stepwise multiple regression. One model retained EFNB2 in combination with glutathione S-transferase alpha 3 and 4, progesterone receptor and glutathione peroxidase 3, resulting in 93% correct predictions when 3 patient and treatment cycle characteristics were included into the model. This large patient group allowed to do an intra-patient analysis for 7 patients, an analysis mimicking the methodology that would ultimately be used in clinical routine. CC related to a SET that did not give pregnancy and CC related to their subsequent frozen/thawed embryos which ended in pregnancy were analyzed. The models obtained in the between-patient analysis were used to rank the oocytes within-patients for their chance to pregnancy and resulted in 86% of correct predictions. In conclusion, prediction models built on selected quantified transcripts in CC might help in the decision making process which is currently only based on subjective embryo morphology scoring. The validity of our current models for routine application still need prospective assessment in a larger and more diverse patient population allowing intra-patient analysis.

show abstract

Section: Discussionmentioning

confidence: 87%

Pregnancy Prediction in Single Embryo Transfer Cycles after ICSI Using QPCR: Validation in Oocytes from the Same Cohort

Wathlet¹,

Adriaenssens²,

Segers³

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Interestingly, our identification of genes modulated in response to GATA4 knockdown in MA-10 cells was not limited to these two steroidogenic targets. We also observed a significant decrease in other components of the steroidogenic pathway including two 3b-HSD isoforms (Hsd3b1 and Hsd3b6), as well as a dramatic decrease in expression of Gsta3 that encodes a glutathione transferase that catalyzes obligatory double-bond isomerizations of steroid precursors, leading to both progesterone and testosterone formation in steroidogenic tissues (Johansson & Mannervik 2001, Raffalli-Mathieu et al 2008, Matsumura et al 2013. These results therefore support a role for GATA4, much like it has been described for NR5A1 (Parker et al 2002), as a transcriptional regulator that sits at the top of the steroidogenic program in Leydig cells.…”

Section: Discussionmentioning

confidence: 92%

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

Bergeron¹,

Nadeau²,

Viger³

2015

Reproduction

View full text Add to dashboard Cite

GATA4 is an essential transcription factor required for the initiation of genital ridge formation, for normal testicular and ovarian differentiation at the time of sex determination, and for male and female fertility in adulthood. In spite of its crucial roles, the genes and/or gene networks that are ultimately regulated by GATA4 in gonadal tissues remain to be fully understood. This is particularly true for the steroidogenic lineages such as Leydig cells of the testis where many in vitro (promoter) studies have provided good circumstantial evidence that GATA4 is a key regulator of Leydig cell gene expression and steroidogenesis, but formal proof is still lacking. We therefore performed a microarray screening analysis of MA-10 Leydig cells in which Gata4 expression was knocked down using an siRNA strategy. Analysis identified several GATA4-regulated pathways including cholesterol synthesis, cholesterol transport, and especially steroidogenesis. A decrease in GATA4 protein was associated with decreased expression of steroidogenic genes previously suspected to be GATA4 targets such as Cyp11a1 and Star. Gata4 knockdown also led to an important decrease in other novel steroidogenic targets including Srd5a1, Gsta3, Hsd3b1, and Hsd3b6, as well as genes known to participate in cholesterol metabolism such as Scarb1, Ldlr, Soat1, Scap, and Cyp51. Consistent with the decreased expression of these genes, a reduction in GATA4 protein compromised the ability of MA-10 cells to produce steroids both basally and under hormone stimulation. These data therefore provide strong evidence that GATA4 is an essential transcription factor that sits atop of the Leydig cell steroidogenic program.

show abstract

“…For the phylogenetic analysis, we also included human GSTA subclass members because previous studies have reported that some GSTA proteins are involved in steroidogenesis in mammals 34 35 36 37 . We found that the mammalian GSTA proteins were clustered in a clade completely different from the Noppera-bo subclade ( Supplementary fig.…”

Section: Resultsmentioning

confidence: 99%

A Halloween gene noppera-bo encodes a glutathione S-transferase essential for ecdysteroid biosynthesis via regulating the behaviour of cholesterol in Drosophila

Enya

Ameku

Igarashi

et al. 2014

Sci Rep

122

View full text Add to dashboard Cite

In insects, the precise timing of moulting and metamorphosis is strictly guided by ecdysteroids that are synthesised from dietary cholesterol in the prothoracic gland (PG). In the past decade, several ecdysteroidogenic enzymes, some of which are encoded by the Halloween genes, have been identified and characterised. Here, we report a novel Halloween gene, noppera-bo (nobo), that encodes a member of the glutathione S-transferase family. nobo was identified as a gene that is predominantly expressed in the PG of the fruit fly Drosophila melanogaster. We generated a nobo knock-out mutant, which displayed embryonic lethality and a naked cuticle structure. These phenotypes are typical for Halloween mutants showing embryonic ecdysteroid deficiency. In addition, the PG-specific nobo knock-down larvae displayed an arrested phenotype and reduced 20-hydroxyecdysone (20E) titres. Importantly, both embryonic and larval phenotypes were rescued by the administration of 20E or cholesterol. We also confirm that PG cells in nobo loss-of-function larvae abnormally accumulate cholesterol. Considering that cholesterol is the most upstream material for ecdysteroid biosynthesis in the PG, our results raise the possibility that nobo plays a crucial role in regulating the behaviour of cholesterol in steroid biosynthesis in insects.

show abstract

Targeting human glutathione transferase A3-3 attenuates progesterone production in human steroidogenic cells

Cited by 24 publications

References 32 publications

Pregnancy Prediction in Single Embryo Transfer Cycles after ICSI Using QPCR: Validation in Oocytes from the Same Cohort

Pregnancy Prediction in Single Embryo Transfer Cycles after ICSI Using QPCR: Validation in Oocytes from the Same Cohort

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

A Halloween gene noppera-bo encodes a glutathione S-transferase essential for ecdysteroid biosynthesis via regulating the behaviour of cholesterol in Drosophila

Contact Info

Product

Resources

About