Project description:Androgens are required for prostate development, growth and physiology, by activating the androgen receptor (AR) upon activation by testosterone and dihydrotestosterone (DHT), the AR undergoes conformational changes, dimerizes and translocates to the cell nucleus regulation important genes releted to cell survival. Understanding the mechanisms of androgen regulation in the prostate gland is important, because the prostate is affected by several different diseases, in particular prostate cancer (PCa). Several ways exist to treat prostate cancer and promote epithelial cell death. Treatments involving androgen manipulation include surgical castration (bilateral orchiectomy), antiandrogens (usually AR antagonists), or substances that inhibit androgen synthesis (5 alpha-reductase inhibitors, gonadotrophin-releasing hormone blockers). 17 beta-estradiol exerts anti-androgen effects by blocking the hypothalamic production of gonadotropin-releasing hormone and thereby inhibiting the production of testosterone by the testes , but also acts locally via interactions with either of the estrogen receptors found in the gland. It is known that the kinetics of apoptosis are different in the rat ventral prostate (VP) of castrated rats (Cas group) and in rats subjected to 17 beta-estradiol high dose (group E2) or their combination (group Cas+E2), with an evident additive effect in the latter situation (Garcia-Florez et al, 2005). The microarray approach was done to figure out what genes are expressed and how the cells of ventral prostate gland responses when the androgen is not available comparing three diferent androgen deprivation methods (sirurgical castration, high dose of 17-beta estradiol and both treatment combined).
Project description:Androgens are required for prostate development, growth and physiology, by activating the androgen receptor (AR) upon activation by testosterone and dihydrotestosterone (DHT), the AR undergoes conformational changes, dimerizes and translocates to the cell nucleus regulation important genes releted to cell survival. Understanding the mechanisms of androgen regulation in the prostate gland is important, because the prostate is affected by several different diseases, in particular prostate cancer (PCa). Several ways exist to treat prostate cancer and promote epithelial cell death. Treatments involving androgen manipulation include surgical castration (bilateral orchiectomy), antiandrogens (usually AR antagonists), or substances that inhibit androgen synthesis (5 alpha-reductase inhibitors, gonadotrophin-releasing hormone blockers). 17 beta-estradiol exerts anti-androgen effects by blocking the hypothalamic production of gonadotropin-releasing hormone and thereby inhibiting the production of testosterone by the testes , but also acts locally via interactions with either of the estrogen receptors found in the gland. It is known that the kinetics of apoptosis are different in the rat ventral prostate (VP) of castrated rats (Cas group) and in rats subjected to 17 beta-estradiol high dose (group E2) or their combination (group Cas+E2), with an evident additive effect in the latter situation (Garcia-Florez et al, 2005). The microarray approach was done to figure out what genes are expressed and how the cells of ventral prostate gland responses when the androgen is not available comparing three diferent androgen deprivation methods (sirurgical castration, high dose of 17-beta estradiol and both treatment combined). Forty-eight 21-day-old male Wistar rats were obtained from the Multidisciplinary Center for Biological Research (CEMIB), University of Campinas. The animals were kept under normal light conditions (12-h light:dark cycle) and received filtered tap water and Purina rodent chow ad libitum. On the 90th day after birth, the rats were divided in four groups (n=3) and assigned to different treatment groups. To cause androgen deprivation, we utilized three different procedures with different effects on epithelial cell apoptosis. Animals in the first group were castrated (Cas) by orchiectomy via scrotal incision under ketamine (150 mg/Kg body weight) and xylazin (10 mg/kg body weight) anesthesia. Animals in the second group received a 25 mg/Kg body weight dose of 17β-estradiol diluted in corn oil (E2 group). The third group received a combination of both treatments (Cas+E2 group) (combined orchiectomy and 17β-estradiol). In the control group (Ct; normal androgen and estrogen), the animals received only the vehicle. Three days after the treatments, the rats were killed by anesthetic overdose, and the ventral prostate was dissected out for the microarray and immunohistochemistry analyses.
Project description:Analysis of hormone effects on irradiated LBNF1 rat testes, which contain only somatic cells except for a few type A spermatgogonia. Rats were treated for 2 weeks with either sham treatment (group X), hormonal ablation (GnRH antagonist and the androgen receptor antagonist flutamide, group XAF), testosterone supplementation (GnRH antagonist and testosterone, group XAT), and FSH supplementation ((GnRH antagonist, androgen receptor antagonist, and FSH, group XAFF). Results provide insight into identifying genes in the somatic testis cells regulated by testosterone, LH, or FSH.
Project description:Proteome characterization of gland confined prostate tumors and non-malignant prostate tissue. Whole cell protein extracts were purified from FFPE radical prostatectomy specimens for a total of 28 tumor samples and 8 adjacent non-malignant prostate tissues. Associated ProteomeXchange identifiers: PXD003430, PXD003452, PXD003515, PXD004132, PXD003615, PXD003636. Quantitative proteomic analysis of adjacent non-malignant prostate tissue (n=8) and gland confined prostate tumors (n=28) obtained from radical prostatectomy procedures; and bone metastatic prostate tumors (n=22) obtained from patients operated to relief spinal cord compression. At the time of surgery, most metastatic patients had relapsed after androgen-deprivation therapy, while 5 were previously untreated.
Project description:A subpopulation of prostate luminal epithelial cells has been previously reported to be sufficient to regenerate prostatic architecture following consecutive rounds of androgen deprivation/repletion. This functional characteristic suggest prostate luminal epithelial cells as the putative cell-of-origin for castration-resistant prostate cancer - which more notizable fenotype is the lack of response to androgen deprivation thereapy. We used microarrays to profile the androgen-induced transcripts in luminal prostate epithelial cells involved in a cycle of prostate regression/regeneration in Hoxb13-rtTA|TetO-H2BGFP transgenic mice.