Evaluation of Tissutal Effects of Finasteride on BPH

Bono, Aldo; Fava, Cesare; Salvadore, Maurizio; Celato, Nicola; Lovisolo, J.

doi:10.1097/00005392-199904020-00456

Cited by 2 publications

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“…Regarding the effects of GnRH agonists on GnRH-R expression in PCa, very heterogeneous findings have been reported in the few published studies dealing with this topic. Bono et al [7] investigated, by immunohistochemistry, the expression of GnRH-R in surgical specimens obtained from PCa patients who were treated for 3 months with neoadjuvant hormonal therapy with leuprolide and the antiandrogen bicalutamide (preceded by a 15 day-long antiandrogen therapy, maximal androgen blockade). The same authors compared their findings with GnRH-R expression found in the samples derived from PCa patients who did not receive any treatment and described a relative treatment-induced decrease in GnRH-R immunoreactivity which, in their opinion, may be due to the analog binding to PCa cells.…”

Section: Discussionmentioning

confidence: 99%

“…The existence of an autocrine/paracrine GnRH system has also been suggested by the detection of GnRH mRNA and protein [1][2][3] and, afterward, by the determination of GnRH-R in various normal and neoplastic extra-pituitary tissues or cell lines [1,[3][4][5][6][7]. In prostate cancer (PCa), the presence of GnRH membrane-binding sites has been demonstrated by a number of laboratories in human cancer specimens, cell lines, and animal experimental models.…”

Section: Introductionmentioning

confidence: 99%

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GnRH receptor expression in human prostate cancer cells is affected by hormones and growth factors

Angelucci

Lama

Iacopino

et al. 2009

Endocr

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GnRH receptors (GnRH-R) have been found in various malignancies, including prostate cancer (PCa). They mediate the direct antitumor effects of GnRH analogs. Nevertheless, few reports concern drug-induced modulation of GnRH-R levels. In this study, we investigated GnRH-R expression in androgen-sensitive (LNCaP) and -insensitive (PC-3) PCa cells treated for 4 and 6 days with a GnRH agonist (Leuprorelin acetate, LA, 10(-11) or 10(-6) M), Dihydrotestosterone (DHT, 10(-9) M), Cyproterone acetate (CA, 10(-7) M), and Epidermal growth factor (EGF, 10 ng/ml), either alone or combined. The RT-PCR analysis showed no variation in GnRH-R mRNA levels of both treated LNCaP and PC-3 cells. On the contrary, immunoblotting indicated that in LNCaP and PC-3 cells, LA upregulated membrane GnRH-R expression (up to 92%). In androgen-sensitive cells, DHT induced a GnRH-R increase (up to 119%) always comparable to that occurring in the presence of CA. GnRH-R upregulation by LA/DHT or CA/DHT association was similar to that promoted by the single agents. In PC-3 cells, EGF upregulated GnRH-R (up to 110%). A prolonged treatment (for 12 days) determined a greater EGF-induced increase in GnRH-R levels (142%). Lower (or no) receptor enhancement occurred when LA and EGF were associated. Our findings indicate that LA post-transcriptionally upregulates its own membrane receptor in androgen-sensitive and -insensitive PCa cells, counteracting the receptor enhancement produced by DHT and EGF. The effects, obtained with a relatively long and continuous treatment, may have implications in the choice of therapy modality with GnRH analogs and may render the receptor a novel therapeutic target, particularly in hormone-refractory PCa.

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Section: Discussionmentioning

confidence: 99%