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Endosulfan elevates testosterone biotransformation and clearance in CD-1 mice
1Department of Toxicology, North Carolina State University, Raleigh 27695, USA.
Toxicology and Applied Pharmacology
|February 18, 1998
Summary
Endosulfan exposure increased testosterone metabolism and urinary elimination in female mice. However, the animals’ natural systems compensated, preventing significant changes in overall hormone levels.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Pharmacology
Background:
- Toxicants can alter endogenous steroid hormone metabolism by inducing hepatic biotransformation enzymes.
- Endosulfan, an organochlorine insecticide, is known to induce hepatic P450 enzymes.
Purpose of the Study:
- To investigate if endosulfan alters testosterone metabolism and clearance rates.
- To determine if these alterations disrupt steroid hormone homeostasis.
Main Methods:
- CD-1 mice were exposed to varying doses of endosulfan.
- Testosterone metabolism pathways (hydroxylation, conjugation, reduction/dehydrogenation) were analyzed.
- Urinary and fecal elimination of radiolabeled androgen were measured.
Main Results:
- Endosulfan increased testosterone hydroxylation and dehydrogenation in female mice, particularly 16 beta-hydroxytestosterone.
- Increased urinary androgen elimination (3.6-fold) was observed in female mice.
- Endosulfan showed higher toxicity in males and did not significantly alter metabolism or elimination in them.
Conclusions:
- Endosulfan exposure enhances testosterone biotransformation and urinary elimination in female mice.
- Homeostatic mechanisms compensate for increased clearance, minimizing effects on serum testosterone levels.