This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gilad, E. Articles by Zisapel, N. Search for Related Content PubMed PubMed Citation Articles by Gilad, E. Articles by Zisapel, N. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL

Interplay between Sex Steroids and Melatonin in Regulation of Human Benign Prostate Epithelial Cell Growth

Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences (E.G., N.Z.), and the Department of Urology, Tel Aviv Medical Center and Sackler Faculty of Medicine (H.M.), Tel Aviv University, Tel Aviv 69978, Israel

Address all correspondence and requests for reprints to: Prof. Nava Zisapel, Ph.D., Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. E-mail: navazis{at}ccsg.tau.ac.il

Human benign prostatic epithelial cells contain functional melatonin receptors that can suppress cell growth and viability. The development of benign prostatic hyperplasia in men is assumed to result from androgen-estrogen imbalance. The impact of sex steroids on melatonin receptors in human benign prostate epithelial cells was investigated. The suppression by melatonin of [³H]thymidine incorporation and cGMP, and the enhancement of cAMP levels in the cells were used as markers of melatonin responses.

Dihydrotestosterone (DHT) and 17ß-estradiol (E₂) separately increased [³H]thymidine incorporation into the cells, but suppressed it when combined. In cells grown with DHT, melatonin responses were extenuated. E₂ greatly reduced the apparent affinity of [¹²⁵I]melatonin binding in these cells without affecting binding site density. In parallel, the ability of melatonin to suppress [³H]thymidine incorporation into the cells was ablated within 1 h after the addition of E₂. The melatonin-mediated increase in cAMP and decrease in cGMP concentrations were also ablated by E₂.

Preincubation of the cells with bis-indolylmaleimide (GF 102903X), a specific inhibitor of protein kinase C, prevented the E₂-mediated inactivation of melatonin binding and the inhibitory action on [³H]thymidine incorporation. Prolonged (18-h) incubation of the cells with phorbol 12-myristate 13-acetate to down regulate protein kinase activity, partially restored [¹²⁵I]melatonin binding and responsiveness in the E₂-treated cells.

These data indicate that 1) DHT and E₂ enhance prostate epithelial cells growth, but reduce cell growth when combined; 2) DHT extenuates the inhibitory effects of melatonin on epithelial cell growth; and 3) E₂ acts to inactivate melatonin receptors and consequently responses in human epithelial benign prostatic hyperplasia cells. This process is probably mediated by protein kinase C.

Together, these results show an interplay between melatonin and sex steroids in the regulation of benign prostatic epithelial cell growth.

This article has been cited by other articles:

				A. GARCÍA RATO, J. GARCÍA PEDRERO, M. A. MARTÍNEZ, B. DEL RIO, P. S. LAZO, and S. RAMOS Melatonin blocks the activation of estrogen receptor for DNA binding FASEB J, May 1, 1999; 13(8): 857 - 868. [Abstract] [Full Text]