Journal ArticleDOI
Three-Month Treatment With a Long-Acting Gonadotropin-Releasing Hormone Agonist of Patients With Benign Prostatic Hyperplasia: Effects on Tissue Androgen Concentration, 5α-Reductase Activity and Androgen Receptor Content
Gianni Forti,R. Salerno,Gloriano Moneti,Sonia Zoppi,Gianna Fiorelli,Tarcisio Marinoni,Alessandro Natali,A. Costantini,Mario Serio,Luciano Martini,Marcella Motta +10 more
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TLDR
It is concluded that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men.Abstract:
The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR) Plasma T, DHT, and 3 alpha-diol levels also were measured Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 001 for DHT and P less than 005 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (010 greater than P greater than 005) The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 005) than that by prostatic tissue of the untreated men (n = 9) The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 005), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 005) than that in the prostatic tissue of the untreated men (n = 8) The mean plasma T levels in treated men decreased from 477 +/- 179 (SD) ng/mL (165 +/- 62 nmol/L) to 027 +/- 042 ng/mL (09 +/- 15 nmol/L) after 1 month of therapy and remained in the castrate range thereafter We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrationsread more
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Androgen Receptor in Prostate Cancer
TL;DR: AR remains important in the development and progression of prostate cancer and the inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.
Journal ArticleDOI
The Androgen Axis in Recurrent Prostate Cancer
James L. Mohler,Christopher W. Gregory,O. Harris Ford,Desok Kim,Catharina M. Weaver,Peter Petrusz,Elizabeth M. Wilson,Frank S. French +7 more
TL;DR: Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation of androgens within prostate cancer tissue at levels sufficient to activate androgenceptor.
Journal ArticleDOI
Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer.
Elahe A. Mostaghel,Stephanie T. Page,Daniel W. Lin,Ladan Fazli,Ilsa Coleman,Lawrence D. True,Beatrice S. Knudsen,David L. Hess,Colleen C. Nelson,Alvin M. Matsumoto,William J. Bremner,Martin E. Gleave,Peter S. Nelson,Peter S. Nelson +13 more
TL;DR: Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment.
Journal ArticleDOI
Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer.
TL;DR: Compounds having a 17-(3-pyridyl) substituent together with a 16,17-double bond have been synthesized, using a palladium-catalyzed cross-coupling reaction of a 17-enol triflate with diethyl(3- pyridol)borane, which are potent inhibitors of human testicular 17 alpha-hydroxylase-C17,20-lyase.
Journal ArticleDOI
Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia.
John D. McConnell,Jean D. Wilson,Fredrick W. George,Jack Geller,Fran Pappas,Elizabeth Stoner +5 more
TL;DR: It is concluded that finasteride causes profound decrease in prostatic dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia.
References
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Craig A. Peters,Patrick C. Walsh +1 more
TL;DR: The findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients, however, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.
Journal ArticleDOI
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TL;DR: A large group of in vivo and in vitro studies indicate that, in adult male mammals, the anterior pituitary and several central nervous structures (in descending order: the hypothalamus, the midbrain, the amygdala,...
Journal ArticleDOI
Treatment of Prostate Cancer with Gonadotropin-Releasing Hormone Agonists
Fernand Labrie,André Dupont,Alain Bélanger,René St-Arnaud,M. Giguere,Yves Lacourcière,Emond J,G. Monfette +7 more
TL;DR: In order to inhibit the action of androgens of both testicular and adrenal origin, GnRH agonists have been administered in association with the pure antiandrogen Flutamide in patients having clinical stage D2 (bone metastases) prostate cancer.