Organochlorine pesticide dieldrin upregulate proximal promoter (PII) driven CYP19A1 gene expression and increases estrogen production in granulosa cells

2021 ◽  
Author(s):  
Deeksha Sharma ◽  
Suman Kumari ◽  
Payal Rani ◽  
Suneel Kumar Onteru ◽  
Partha Roy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Organochlorine Pesticide ◽  
Granulosa Cells ◽  
Proximal Promoter ◽  
Estrogen Production

scholarly journals Corticotropin-Releasing Factor Inhibits Luteinizing Hormone-Stimulated P450c17 Gene Expression and Androgen Production by Isolated Thecal Cells of Human Ovarian Follicles1

1998 ◽  
Vol 83 (2) ◽  
pp. 448-452
Author(s):  
H. F. Erden ◽  
I. H. Zwain ◽  
H. Asakura ◽  
S. S. C. Yen
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Inhibitory Effect ◽  
Corticotropin Releasing Factor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Messenger Ribonucleic Acid ◽  
Estrogen Production ◽  
Thecal Cells ◽  
Crf System

Recently, we reported that the thecal compartment of the human ovary contains a CRF system replete with gene expression and protein for corticotropin-releasing factor (CRF), CRF-Receptor 1 (CRF-R1), and the blood-derived high affinity CRF-binding protein (CRF-BP). Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17α-hydroxylase messenger ribonucleic acid (mRNA) and proteins in thecal cells with follicular maturation suggest that the intraovarian CRF system may play an autocrine role regulating androgen biosynthesis, with a downstream effect on estrogen production by granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of plasma-derived CRF-BP by virtue of its localization of protein, but not transcript in thecal cells and its ability to compete with CRF for the CRF receptor. To further these findings, in the present study we have examined the effect of CRF on LH-stimulated 17α-hydroxylase (P450c17) gene expression and androgen production by isolated thecal cells from human ovarian follicles (11–13 mm). During the 48-h culture, addition of LH (10 ng/mL) to the medium increased by 5- and 6-fold dehydroepiandrosterone and androstenedione production by thecal cells. Remarkably, the LH-stimulated, but not basal, androgen production was inhibited by CRF in a time- and dose-dependent manner. The half-maximal (ID50) effect dose of CRF occurred at 5 × 10−8 mol/L, and at a maximal concentration of 10−6 mol/L, CRF completely inhibited LH-stimulated androgen production. This inhibitory effect of CRF became evident at 12 h (45%), and by 24 h the effect was more pronounced, with a 70% reduction from baseline. As determined by Northern analyses, CRF dose dependently decreased LH-stimulated P450c17 mRNA levels, with a maximal inhibition of 85% P450c17 gene expression at a CRF concentration of 10−6 mol/L. With the addition of 10−6 mol/L of the antagonist α-helical CRF-(9–41), the inhibitory effect of CRF was partially reversed for both P450c17 mRNA (75%) and androgen production (50%), indicating the CRF-R1-mediated event. In conclusion, the present study demonstrated a potent inhibitory effect of CRF on LH-stimulated dehydroepiandrosterone and androstenedione production that appears to be mediated through the reduction of P450c17 gene expression. Thus, the ovarian CRF system may function as autocrine regulators for androgen biosynthesis in the thecal cell compartment to maintain optimal substrate for estrogen biosynthesis by granulosa cells. Further studies to define the role of CRF-BP in the endocrine modulation of the intraovarian CRF system are needed.

scholarly journals Epigenetic Changes of the Cyp11a1 Promoter Region in Granulosa Cells Undergoing Luteinization During Ovulation in Female Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3344-3354 ◽  
Author(s):  
Maki Okada ◽  
Lifa Lee ◽  
Ryo Maekawa ◽  
Shun Sato ◽  
Takuya Kajimura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Granulosa Cells ◽  
Chromatin Immunoprecipitation ◽  
Promoter Region ◽  
Binding Protein ◽  
Female Rats ◽  
Proximal Promoter ◽  
Lh Surge ◽  
Enhancer Binding Protein

The ovulatory LH surge induces rapid up-regulation of Cyp11a1 in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic controls including histone modifications and DNA methylation in the promoter region are associated with the rapid increase of Cyp11a1 gene expression after LH surge. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and 4 h and 12 h after human (h)CG injection. Cyp11a1 mRNA levels rapidly increased after hCG injection, reached a peak at 4 hours, and then remained elevated until 12 hours. DNA methylation status in the Cyp11a1 proximal promoter region was hypomethylated and did not change at any of the observed times after hCG injection. Chromatin immunoprecipitation assays revealed that the levels of trimethylation of lysine 4 on histone H3 (H3K4me3), an active mark for transcription, increased, whereas the levels of H3K9me3 and H3K27me3, which are marks associated with repression of transcription, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin condensation, which was analyzed using deoxyribonuclease I, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin immunoprecipitation assays also showed that the binding activity of CAATT/enhancer-binding protein-β to the Cyp11a1 proximal promoter increased after hCG injection. Luciferase assays revealed that the CAATT/enhancer-binding protein-β-binding site had transcriptional activity and contributed to basal and cAMP-induced Cyp11a1 expression. These results suggest that changes in histone modification and chromatin structure in the Cyp11a1 proximal promoter are involved in the rapid increase of Cyp11a1 gene expression in GCs undergoing luteinization during ovulation.

scholarly journals Repression of ESR1 through Actions of Estrogen Receptor Alpha and Sin3A at the Proximal Promoter

2009 ◽  
Vol 29 (18) ◽  
pp. 4949-4958 ◽  
Author(s):  
Stephanie J. Ellison-Zelski ◽  
Natalia M. Solodin ◽  
Elaine T. Alarid
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Transcriptional Repression ◽  
Estrogen Receptor Alpha ◽  
Proximal Promoter ◽  
Receptor Alpha ◽  
Expression Of Genes ◽  
Activation Of Transcription

ABSTRACT Gene expression results from the coordinated actions of transcription factor proteins and coregulators. Estrogen receptor alpha (ERα) is a ligand-activated transcription factor that can both activate and repress the expression of genes. Activation of transcription by estrogen-bound ERα has been studied in detail, as has antagonist-induced repression, such as that which occurs by tamoxifen. How estrogen-bound ERα represses gene transcription remains unclear. In this report, we identify a new mechanism of estrogen-induced transcriptional repression by using the ERα gene, ESR1. Upon estrogen treatment, ERα is recruited to two sites on ESR1, one distal (ENH1) and the other at the proximal (A) promoter. Coactivator proteins, namely, p300 and AIB1, are found at both ERα-binding sites. However, recruitment of the Sin3A repressor, loss of RNA polymerase II, and changes in histone modifications occur only at the A promoter. Reduction of Sin3A expression by RNA interference specifically inhibits estrogen-induced repression of ESR1. Furthermore, an estrogen-responsive interaction between Sin3A and ERα is identified. These data support a model of repression wherein actions of ERα and Sin3A at the proximal promoter can overcome activating signals at distal or proximal sites and ultimately decrease gene expression.

scholarly journals Endothelin (ET)-1 and ET-3 inhibit estrogen and cAMP production by rat granulosa cells in vitro

1998 ◽  
Vol 157 (2) ◽  
pp. 209-215 ◽  
Author(s):  
AE Calogero ◽  
N Burrello ◽  
AM Ossino
Keyword(s):  
Granulosa Cells ◽  
Ovarian Function ◽  
Biological Effects ◽  
Female Rats ◽  
Dependent Manner ◽  
Camp Production ◽  
Inhibitory Effects ◽  
Ovarian Steroidogenesis ◽  
Estrogen Production ◽  
Etb Receptor

Endothelin (ET)-1 and ET-3, two peptides with a potent vasoconstrictive property, produce a variety of biological effects in different tissues by acting through two different receptors, the ET-1 selective ET(A) receptor and the non-selective ETB receptor. An increasing body of literature suggests that ET-1 acts as a paracrine/autocrine regulator of ovarian function. Indeed, ETB receptors have been identified in rat granulosa cells and ET-1 is a potent inhibitor of progesterone production. In contrast, inconsistent data have been reported about the role of ET-1 on estrogen production and the effects of ET-3 are not known. Therefore, the present study was undertaken to evaluate the effects of ET-1 and ET-3 on estrogen and cAMP production, and the receptor type involved. Given that prostanoids modulate ovarian steroidogenesis and that many actions of ETs are mediated by these compounds, we also evaluated whether the effects of ETs on estrogen and cAMP production might be prostanoid-mediated. ET-1, ET-3, and safarotoxin-S6c (SFX-S6c), a selective ETB receptor agonist, inhibited basal estrogen production by granulosa cells obtained from immature, estrogen-primed female rats, in a concentration-dependent manner. All three peptides were also capable of inhibiting the production of estrogen stimulated by a half-maximal (1 mIU/ml) and a maximally stimulatory (3 mIU/ml) concentration of FSH, ET-1 and ET-3 dose-dependently suppressed basal and FSH (1 mIU/ml)-stimulated cAMP production. ET-3 and SFX-S6c were significantly more potent than ET-1 in suppressing estrogen production, suggesting that this effect was not mediated by the ET(A) receptor. Indeed, BQ-123, a selective ET(A) receptor antagonist, did not influence the inhibitory effects of ET-1 and ET-3 on basal and FSH-stimulated estrogen release. To determine a possible involvement of prostanoids, we evaluated the effects of maximally effective concentrations of ET-1 and ET-3 on estrogen and cAMP production in the presence of indomethacin, a prostanoid synthesis inhibitor. This compound did not have any effect on the suppressive effects of ETs on basal or FSH (1 mIU/ml)-stimulated estrogen or cAMP production. In conclusion, ET-1 and ET-3 were able to inhibit estrogen and cAMP production by rat granulosa cells, indicating that the inhibitory effects of ETs on ovarian steroidogenesis are not limited to progesterone biosynthesis. This effect does not appear to be mediated by prostanoids or by the classical ET(A) and ETB receptors, at least under these experimental conditions.

scholarly journals Granulosa cells from human primordial and primary follicles show differential global gene expression profiles

2018 ◽  
Vol 33 (4) ◽  
pp. 666-679 ◽  
Author(s):  
E H Ernst ◽  
S Franks ◽  
K Hardy ◽  
P Villesen ◽  
K Lykke-Hartmann
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression

Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation

2005 ◽  
Vol 288 (5) ◽  
pp. F899-F909 ◽  
Author(s):  
Zubaida Saifudeen ◽  
Susana Dipp ◽  
Hao Fan ◽  
Samir S. El-Dahr
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Binding ◽  
Spatial Organization ◽  
Kidney Development ◽  
Collecting Duct ◽  
Proximal Promoter ◽  
Bradykinin B2 Receptor ◽  
Nephron Differentiation ◽  
Terminal Nephron

Despite a wealth of knowledge regarding the early steps of epithelial differentiation, little is known about the mechanisms responsible for terminal nephron differentiation. The bradykinin B2 receptor (B2R) regulates renal function and integrity, and its expression is induced during terminal nephron differentiation. This study investigates the transcriptional regulation of the B2R during kidney development. The rat B2R 5′-flanking region has a highly conserved cis-acting enhancer in the proximal promoter consisting of contiguous binding sites for the transcription factors cAMP response element binding protein (CREB), p53, and Krüppel-like factor (KLF-4). The B2R enhancer drives reporter gene expression in inner medullary collecting duct-3 cells but is considerably weaker in other cell types. Site-directed mutagenesis and expression of dominant negative mutants demonstrated the requirement of CREB DNA binding and Ser-133 phosphorylation for optimal enhancer function. Moreover, helical phasing experiments showed that disruption of the spatial organization of the enhancer inhibits B2R promoter activity. Several lines of evidence indicate that cooperative interactions among the three transcription factors occur in vivo during terminal nephron differentiation: 1) CREB, p53, and KLF-4 are coexpressed in B2R-positive differentiating cells; 2) the maturational expression of B2R correlates with CREB/p53/KLF-4 DNA-binding activity; 3) assembly of CREB, p53, and KLF-4 on chromatin at the endogenous B2R promoter is developmentally regulated and is accompanied by CBP recruitment and histone hyperacetylation; and 4) CREB and p53 occupancy of the B2R enhancer is cooperative. These results demonstrate that combinatorial interactions among the transcription factors, CREB, p53, and KLF-4, and the coactivator CBP, may be critical for the regulation of B2R gene expression during terminal nephron differentiation.

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