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DDT increases hepatic testosterone metabolism in rats
Adolfo Sierra-Santoyo1, Manuel Hernández, Arnulfo Albores
1Sección de Toxicología, Cinvestav-IPN, PO Box 14-740, Mexico DF, Mexico.
Archives of Toxicology
|September 17, 2004
Summary
Technical-grade DDT disrupts liver testosterone metabolism in rats, altering hormone profiles in a sex-dependent manner. This endocrine disruptor affects androgen pathways and reduces metabolic differences between males and females.
Area of Science:
- Endocrinology
- Toxicology
- Biochemistry
Background:
- DDT and its metabolites are recognized endocrine disruptors with the potential to induce hormone-dependent diseases.
- Understanding DDT's impact on hormone metabolism is crucial for assessing its health risks.
Purpose of the Study:
- To investigate the effects of technical-grade DDT on hepatic testosterone metabolism in male and female rats.
- To analyze alterations in testosterone hydroxylase activity ratios as indicators of endocrine disruption.
Main Methods:
- Rats were administered single oral doses of technical-grade DDT (0-100 mg/kg).
- Hepatic microsomes were incubated with [4-14C]-testosterone.
- Metabolites were separated using thin-layer chromatography and quantified via radio scanning.
Main Results:
- DDT exposure significantly altered testosterone biotransformation and metabolite profiles in a sex-specific manner.
- In males, DDT increased the 6beta-OHT ratio while decreasing AD, 2alpha-OHT, and 16alpha-OHT.
- In females, DDT increased 6beta-OHT and 6alpha-OHT ratios while decreasing 7alpha-OHT and AD. The 6alpha-/15alpha-OHT ratio, indicative of demasculinization, increased in males.
Conclusions:
- Technical-grade DDT disrupts hepatic sexual dimorphism in testosterone metabolism.
- The observed alterations suggest DDT's potential to induce demasculinization in males and a shift towards a more masculine pattern in females.
- DDT reduces the metabolic distinctions between male and female testosterone processing.