Back to Search
Start Over
Disruption of LH-induced testosterone biosynthesis in testicular Leydig cells by triclosan: Probable mechanism of action
- Source :
- Toxicology. 250:124-131
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Triclosan (TCS) is an antimicrobial chemical widely used in different commercial preparations. The present study demonstrated the mechanism of action of TCS-induced anti-androgenicity in rat Leydig cells. Treatment of purified cells with increasing concentrations of TCS (0.001, 0.01, 0.1, 1 and 10 microM) resulted in a significantly decreased activity of adenylyl cyclase enzyme which was followed by a decreased synthesis of cAMP. This decreased cAMP level resulted in the disruption of entire steroidogenic cascade causing a depressed synthesis of testosterone. However, TCS-induced decrease in the production of testosterone returned to normalcy when cells were treated with forskolin (an adenylyl cyclase activator). Transcription followed by translational of four prominent steroidogenic enzyme/proteins, cytochrome P450 side chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and steroidogenic acute regulatory (StAR) protein, also decreased in a dose-dependent manner in TCS-treated Leydig cells as determined by RT-PCR, enzyme assay and Western blot. These results suggested that the disruption of the activity of adenylyl cyclase enzyme by TCS in turn leads to the disruption of intermediate steroidogenic cascade causing a depressed testosterone production. The study further confirmed the anti-androgenic activity of TCS in Leydig cells with highest effective concentration at 1 microM.
- Subjects :
- Male
endocrine system
medicine.medical_specialty
17-Hydroxysteroid Dehydrogenases
Blotting, Western
Tetrazolium Salts
Cell Separation
Endocrine Disruptors
Toxicology
ADCY10
Adenylyl cyclase
chemistry.chemical_compound
Internal medicine
Cyclic AMP
medicine
Animals
Testosterone
Rats, Wistar
Cells, Cultured
Chromatography, High Pressure Liquid
Forskolin
Dose-Response Relationship, Drug
biology
Leydig cell
Reverse Transcriptase Polymerase Chain Reaction
Cholesterol side-chain cleavage enzyme
fungi
Leydig Cells
Luteinizing Hormone
3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
Triclosan
Enzyme assay
Rats
Thiazoles
Endocrinology
medicine.anatomical_structure
chemistry
Mechanism of action
Anti-Infective Agents, Local
biology.protein
medicine.symptom
Luteinizing hormone
Adenylyl Cyclases
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 250
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....dee803da6d4dd48e102d1bfd02a1d2bb