Related Experiment Video

Updated: Sep 21, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

Endotoxin induced TLR4 signaling downregulates CYP19A1 expression through CEBPB in buffalo granulosa cells

Vengala Rao Yenuganti1, Ravinder1, Dheer Singh1

  • 1Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001, Haryana, India.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|April 17, 2017
PubMed

Insights

Bacterial endotoxin (LPS) reduces estradiol by downregulating CYP19A1 gene expression in buffalo granulosa cells. This occurs via the TLR4 pathway, increasing CEBPB binding to the CYP19A1 promoter.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cellular Signaling

Background:

  • Estrogen is crucial for ovarian follicle development.
  • Bacterial infections, like E. coli endotoxin (LPS), can suppress estradiol production.
  • The precise molecular mechanisms behind LPS-induced CYP19A1 downregulation remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of LPS-mediated downregulation of CYP19A1 gene expression.
  • To determine the role of TLR4 signaling in this process.
  • To identify potential regulatory factors involved in LPS-induced suppression of estradiol synthesis.

Main Methods:

  • Cultured buffalo granulosa cells were treated with LPS and a TLR4 inhibitor (OxPAPC).
  • CYP19A1 and CEBPB gene expression levels were analyzed.
  • CEBPB binding to the CYP19A1 proximal promoter (CYP19A1 PII) was assessed using chromatin immunoprecipitation.

Main Results:

  • LPS treatment significantly decreased CYP19A1 gene expression.
  • Inhibitor studies confirmed the involvement of TLR4 in LPS-induced CYP19A1 downregulation.
  • LPS increased cellular and nuclear CEBPB levels and enhanced CEBPB binding to the CYP19A1 promoter, effects attenuated by the TLR4 inhibitor.

Conclusions:

  • CEBPB is identified as a potential regulator in the LPS-mediated downregulation of CYP19A1.
  • This mechanism contributes to the decline in 17-beta estradiol levels observed in buffalo granulosa cells during infection.
Keywords:
ChIPLAPLPSOxPAPCProximal promoter

More Related Videos

A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells05:36

A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells

Published on: September 6, 2018

A Modified Co-Culture System for Understanding Granulosa-Theca Cell Interactions in the Bovine Ovary07:03

A Modified Co-Culture System for Understanding Granulosa-Theca Cell Interactions in the Bovine Ovary

Published on: September 19, 2025

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...