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Estrogenic action of commonly used fragrant agent citral induces prostatic hyperplasia

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Summary

A rat model for benign prostatic hyperplasia in man (BPH) was investigated. Citral treatment of male Copenhagen rats for 4 months via the transdermal route resulted in a marked hyperplasia of glandular epithelium and interglandular stroma in the ventral prostate. Despite the cellular hyperplasia there was not a significant increase in prostate weight. Investigations of the mechanism of action of citral showed that application of citral directly to the vagina in female, ovariectomized rats resulted in an increased proliferation of vaginal epithelium and a significant increase in the BrdUrd incorporation in vaginal epithelial cells, in short a similar effect to that of estrogen application. In an in vitro assay citral proved to inhibit estrogen binding to estrogen receptors, while no such inhibition was observed with testosterone for androgen receptors. These observations together with the estrogen implication in the BPH and the reported incidence of gynccomastia following exposure to geraniol, a precursor of citral, strongly suggest that the prostatic hyperplasia-inducing capacity of citral may be due to its estrogenic action.

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References

  1. Abramovici A, Sandbank U (1988) The mortician's mystery solved? N Engl J Med 319: 1157

    Google Scholar 

  2. Abramovici A, Servadio C, Sandbank U (1985) Benign hyperplasia of ventral prostate in rats induced by a monoterpene (preliminary report). Prostate 7: 389

    Google Scholar 

  3. Abramovici A, Servadio C, Shmuely J, Sandbank U (1987) Experimental induction of atypical hyperplasia in rat ventral prostat. In: Murphy GP, Khoury S, Küss R, Chatelain C, Denis L (eds) Prostate cancer, part A: Research, endocrine treatment and histopathology. Liss, New York, p 559

    Google Scholar 

  4. Berry SJ, Coffey DS, Walsh PC, Ewing LL (1984) The development of human prostatic hyperplasia with age. J Urol 132: 474

    Google Scholar 

  5. Berry SJ, Coffey DS, Ewing LL (1985) A comparison of human and canine benign prostatic hyperplasia. In: Bruchovsky N, Chapdelaine A, Neumann F (eds) Regulation of androgen action. Brückner, Berlin (West), p 59

    Google Scholar 

  6. Berry SJ, Strandberg JD, Saunders WJ, Coffey DS (1986) Development of canine benign prostatic hyperplasia with age. Prostate 9: 363

    Google Scholar 

  7. Brendler CB, Berry SJ, Ewing LL, McCullough AR, Cochran RC, Strandberg JD, Zirkin BR, Coffey DS, Wheaton L, Hiler M, Bordy MJ, Niswender GD, Scott WW, Walsh PC (1983) Spontaneous benign prostatic hyperplasia in the beagle. Age-associated changes in serum hormone levels, and the morphology and secretory function of the canine prostate. J Clin Invest 71: 1114

    Google Scholar 

  8. Chung LWK, Matsuura J, Runner MN (1984) Tissue interactions and prostatic growth: I. Induction of adult mouse prostatic hyperplasia by fetal urogenital sinus implants. Biol Repord 31: 155

    Google Scholar 

  9. Connor MJ (1991) Modulation of tumor promotion in mouse skin by the food additive citral (3,7-dimethyl-2,6-octadienal). Cancer Lett 56: 25

    Google Scholar 

  10. DeKlerk DP, Coffey DS, Ewing LL, McDermontt IR, Reiner WG, Robinson CH, Scott WW, Strandberg JD, Talalay P, Walsh PC, Wheaton LG, Zirkin BR (1979) Comparison of spontaneous and experimentally induced canine prostatic hyperplasia. J Clin Invest 64: 842

    Google Scholar 

  11. Diliberto JJ, Usha G, Birnbaum LS (1988) Disposition of citral in male Fisher rats. Drug Metab Dispos 16: 721

    Google Scholar 

  12. Habenicht U-F, ElEtreby MF (1988) The periurethral zone of the prostate of the cynomolgus monkey is the most sensitive prostate part for an estrogenic stimulus. Prostate 13: 305

    Google Scholar 

  13. Habenicht U-F, ElEtreby MF (1989) Selective inhibition of androstenedione-induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-methyl-ADD). Prostate 14: 309

    Google Scholar 

  14. Habenicht U-F, Schwarz K, Neumann F, ElEtreby MF (1987) Induction of estrogen-related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonization by the aromatase inhibitor 1-methyl-androsta-1,4-diene 3,17-dione. Prostate 11: 313

    Google Scholar 

  15. Isaacs JT (1984) Common characteristics of human and canine benign prostatic hyperplasia. Prog Clin Biol Res 145: 217

    Google Scholar 

  16. Juniewicz PE, Lemp BM, Barbolt TA, LaBrie TK, Batzold FH, Reel JR (1989) Dose-dependent hormonal induction of benign prostatic hyperplasia (BPH) in castrated dogs. Prostate 14: 341

    Google Scholar 

  17. Juniewicz PE, Lemp BM, Barbolt TA, Labrie TK, McCarty M, Reel JR, Batzold FH (1990) Effect of steroidal androgen receptor antagonist Win 49,596 on steroid induced benign prostatic hyperplasia in the castrate beagle dog. Prostate 16: 1

    Google Scholar 

  18. Kozák I, Bartsch W, Krieg M, Voigt K-D (1982) Nuclei of stroma: site of highest estrogen concentration in human prostatic hyperplasia. Prostate 3: 433

    Google Scholar 

  19. McNeal JE (1983) Relationship of the origin of benign prostatic hypertrophy to prostatic structure of man and other mammals. In: Hinman F Jr (ed) Benign prostatic hyperplasia. Springer, New York, p 153

    Google Scholar 

  20. Sandbank M, Abramovici A, Ben-David E (1988) Sebaceous gland hyperplasia following application of citral. An ultrastructural study. Am J Dermatopathol 10: 415

    Google Scholar 

  21. Schulze H, Claus S (1990) Histological localization of estrogen receptors in normal and diseased human prostates by immunocytochemistry. Prostate 16: 331

    Google Scholar 

  22. Servadio C, Abramovici A, Sandbank U, Savion M, Rosen M (1986) Early stages of the pathogenesis of rat ventral prostate hyperplasia induced by citral. Eur Urol 12: 195

    Google Scholar 

  23. Sikes RA, Thomsen S, Petrow V, Neubauer BL, Chung LWK (1990) Inhibition of experimentally induced mouse prostatic hyperplasia by castration or steroid antagonist administration. Biol Reprod 43: 353

    Google Scholar 

  24. Walsh PC, Wilson JD (1976) The induction of prostatic hypertrophy in the dog with androstanediol. J Clin Invest 57: 1093

    Google Scholar 

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Geldof, A.A., Engel, C. & Rao, B.R. Estrogenic action of commonly used fragrant agent citral induces prostatic hyperplasia. Urol. Res. 20, 139–144 (1992). https://doi.org/10.1007/BF00296526

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