Letrozole effect in murine ventral prostate
Efectos del letrozol de la próstata ventral de murinos
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The prostate gland is regulated by steroid hormones and complex interactions based on a subtle balance between androgen and estrogen (E2) regulate prostatic development and physiology. Interestingly, the changes in steroid hormone levels at old ages affect the hormonal milieu and contribute to the evolution of the pathological changes of the gland. We have analyzed the effects of letrozole, an aromatase inhibitor, on the structure in the ventral prostate of control and castrated adult rats. The results demonstrated alterations in prostate physiology after letrozole treatment. Serum levels of testosterone, prostate weight and proliferative index in luminal and basal cells were increased. Estrogen serum levels were not altered dramatically, in contrast to slight increase in gonadotrophin hormones seen in the castrated animals. Castration did not alter the proliferation index of basal cells. Reorganization of tissue compartments was seen with significant increase in letrozole treated animals. A decrease in androgen receptor expression was seen 21-days after the beginning of treatment with letrozole. These results were confirmed by immunohistochemistry. These results reveal new aspects in the relationship between androgen receptor and steroid metabolism in the prostate gland, demonstrating that alteration in hormone levels during a short time period induces significant alterations in prostate homeostasis.
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Imamov, O., Morani, A., Shim, G.J., Omoto, Y., Thulin-Andersson, C., Warner, M., Gustafsson, J.A. Estrogen receptor beta regulates epithelial cellular differentiation in the mouse ventral prostate. Proceedings of the National Academy of Sciences USA. 2004. 101; 9375-9380.
Omoto, Y., Imamov, O., Warner, M., Gustafsson, J.A. Estrogen receptor alpha and imprinting of the neonatal mouse ventral prostate by estrogen. Proceedings of the National Academy of Sciences USA. 2005. 102; 1484-1489.
Takase, Y., Lévesque, M.H., Luu-The, V., El-Alfy, M., Labrie, F., Pelletier, G. Expression of Enzymes Involved in Estrogen Metabolism in Human Prostate. Journal of Histochemistry & Cytochemistry. 2006. 54; 911–921.
Fischer, C.R. Characterization of mice deficient in Aromatase (Arko) because of targered disruption of the Cyp 19 gene. Proceedings of the National Academy of Sciences USA. 1998. 95; 6965-6970.
Ellem, S.J., Schmitt, J.F., Pedersen, J.S., Frydenberg, M., Risbridger, G.P. Local aromatase expression in human prostate is altered in malignancy. Journal of Clinical Endocrinology and Metabolism. 2004. 89, 2434-41.
Carreau, S., Lambard, S., Delalande, C., Denis-Galeraud, I., Bilinska, B., Bourguiba, S. Aromatase expression and role of estrogens in male gonad: a review. Reproductive Biology and Endocrinology. 2003. 1; 35-41.
Simpson, E.R., Mahendroo, M.S., Means, G.D., Kilgore, M.W., Hinshelwood, M.M., Graham-Lorence, S., Amarneh, B., It, Y., Fischer, C.R., Dodson, M.M., Mendelson C.R., Bulun, S.E. Aromatase cytochrome p450, the enzyme responsible for estrogen biosynthesis. Endocrine Reviews. 1994. 15; 342-355.
Li, X. Altered structure and function of reproductive organs in transgenic male mice over expressing human aromatase. Endocrinology. 2001. 142; 2435-2442.
McPherson, S.J., Wang, H., Jones, M.E, Pedersen, J, Iismaa, T.P., Wreford, N., Simpson, E.R., Risbridger, G.P. Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland. Endocrinology. 2001. 142; 2458-2467.
Ho, S.M., Lee, K.F., Lane, K. Neoplastic transformation of the prostate. In: Naz RK, ed. Prostate: basic and clinical aspects. New York: CRC Press. 1997; 73-114.
Prins, G.S., Birch, L., Greene, G.L. Androgen receptor localization in different cell types of the adult rat prostate. Endocrinology. 1991. 129; 3187-3199.
Prins, G.S., Birch, L. Immunocytochemical analysis of androgen receptor along the ducts of the separate rat prostate lobes after androgen withdrawal and replacement. Endocrinology. 1993. 132; 169-178.
Prins, G.S., Birch, L. The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen. Endocrinology. 1995. 136; 1303-1314.
Tobin, V.A., Canny, B.J. The regulation of gonadotropin-releasing hormone-induced calcium signals in male rat gonadotrophs by testosterone Is mediated by dihydrotestosterone. Endocrinology. 1998. 139; 1038-1045.
Bhatnagar, A.S, Batzl, C., Hausler, A., Nogues, V. The role of estrogen in the feedback regulation of follicle-stimulating hormone secretion in the female rat. The Journal of Steroid Biochemistry and Molecular Biology. 1993. 47; 161-166.
Behmer, A.O., Tolosa, E.M.C., Neto, A.G.F. Manual de práticas para histologia normal e patológica. São Paulo: Edart-Edusp. 1976.
Mistry, P., Griffiths, K., Maynard, P.V. Endogenous C19-steroids and oestradiol levels in human primary breast tumour tissues and their correlation with androgen and oestrogen receptors. Journal of Steroid Biochemistry. 1986. 6; 1117-1125.
Macedo, L.F., Guo, Z., Tilghman, S.L., Sabnis, G.J., Qiu, Y., Brodie, A. Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Research. 2006. 66 ; 7775-7782.
Weihua, Z., Makela, S., Andersson, L.C., Salmi, S., Saji, S., Webster, J.L., Jensen, E.V., Nilsson, S., Warner, M., Gustafsson, J.A. A role for estrogen receptor b in the regulation of growth of the ventral prostate. Proceedings of the National Academy of Sciences USA. 2001. 98 ; 6330-6335.
