Citral and testosterone interactions in inducing benign and atypical prostatic hyperplasia in rats

Dov Engelstein, Joseph Shmueli, Sela Bruhis, Ciro Servadio, Armand Abramovici

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19 Scopus citations


Citral is a monoterpene in wide use as an aromatic supplement in the cosmetics and food industries. Previous studies in our laboratory have shown that cutaneous application of citral on adolescent rats may induce benign prostatic hyperplasia (BPH)-like and even atypical hyperplastic changes in the ventral lobes. In the present study we investigate the possible interactions between citral and serum testosterone levels on the induction of hyperplastic changes in the ventral prostate of adolescent rats. In addition, the study includes a comparative analysis of normal intact rats showing circadian variations of serum testosterone levels and rats in whom this rhythmic pattern was abolished either by excessive supplementation of exogenous androgen or by castration. Our results demonstrate an induction of benign as well as atypical prostatic hyperplasia following citral application. The most severe atypical changes were noted in the citral-treated rats with high serum testosterone levels. Although the mechanism of action of citral is yet unknown, the present results suggest a synergism between citral and testosterone resulting in hyperplastic changes in the rat ventral prostate. In addition, the results reconfirm that serum testosterone levels fluctuate according to a circadian rhythm in intact young and adolescent male rats. The application of citral tends to lower the morning circadian peaks, and the circadian pattern was abolished in orchiectomized rats and in those treated with testosterone implants.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalComparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology
Issue number2
StatePublished - Oct 1996
Externally publishedYes

Bibliographical note

Funding Information:
We wish to acknowledge the research support from the National Security Agency. James Chrissis, Sidney Kissin and Lorin Lund are thanked for their invaluable input during the entire study. Any opinions expressed here are those of the authors and do not represent their affilia- tions, both present and past.


  • circadian
  • citral
  • hyperplasia
  • prostate
  • rat
  • testosterone


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