Endocrine pathology of estrogens: species differences

Area of Science:

• Toxicology
• Endocrinology
• Comparative Medicine

Background:

• Clinical use of estrogens is linked to severe adverse effects, necessitating ongoing toxicological evaluation.
• Estrogenic compounds exhibit qualitatively similar effects across species at high doses, but toxicity correlates with potency.

Purpose of the Study:

• To review the experimental toxicology of estrogens and their effects across different species.
• To investigate interspecies variations in estrogen and antiestrogen activity and their toxicological implications.

Main Methods:

• Comparative analysis of estrogen toxicity in various animal models, including rodents (rats, mice) and carnivores (cats, ferrets, dogs).
• Observation of effects on reproductive, mammary, and endocrine tissues, as well as organ weights and growth rates.
• Assessment of hematological changes, liver damage, and bone marrow depression.
• Evaluation of antiestrogen effects on estrogen toxicity in specific species.

Main Results:

• Toxicity is generally related to estrogenic potency, with carnivores being more susceptible than rodents.
• Observed effects include changes in reproductive and endocrine tissues, altered organ weights, decreased growth rates in rodents, and liver damage.
• Hematological effects ranged from anemia in rats to bone marrow depression in dogs and ferrets, with death linked to hemorrhage.
• Antiestrogens modulated estrogen toxicity in rats but not ferrets, highlighting species-specific responses.

Conclusions:

• Interspecies differences, particularly in the hypothalamic-pituitary axis, significantly influence the differential activities of estrogens and antiestrogens.
• The predictive value of animal studies for human responses to estrogens and antiestrogens has been limited.
• Understanding species-specific toxicological profiles is crucial for assessing the risks associated with estrogenic compounds.