雄激素受体调控基因组表达与去势抵抗性前列腺癌关系探索

目的 探索雄激素受体调控基因与前列腺癌发生去势抵抗的关系.方法 选取80例经病理检查和临床资料证实并采用内分泌治疗的前列腺癌患者,随访获取发生去势抵抗时间,定量即时聚合酶链锁反应(qRT-PCR)检测确诊时穿刺标本的六个雄激素受体调控基因KLK3(PSA),PMEPA1,NKX3.1,ODC1,AMD1和ERG表达并分...     

不同去势方法对晚期前列腺癌患者胰岛素抵抗的影响

背景与目的：雄激素阻断治疗是晚期前列腺癌最主要的治疗手段．临床上发现接受雄激素阻断治疗的晚期前列腺癌患者常常会发生糖耐量的异常．然而间歇性或持续性雄激素阻断对糖耐量的影响是否不同,国内外报道较少。本研究探讨间歇性雄激素阻断（intermittent androgen blockade,IAB）和持续性雄激素阻断即手术去势与晚期前列腺癌患者胰岛素抵抗的相关性。方法：根据体重指数（bodymassindex,BMI）及治疗方式,将139例晚期前列腺癌患者分为4组。高BMI去势组（A组）30例,BMI≥24kg／m^2,采用手术去势治疗;高BMI间歇阻断组（B组）32例,BMI≥24kg／m^2,采用IAB治疗;低BMI去势组（C组）37例,BMI〈24kg／m^2,采用手术去势治疗;低BMI间歇阻断组（D组）40例,BMI〈24kg／m2,采用IAB治疗。所有患者在治疗前、治疗6个月、治疗12个月时分别测定空腹血糖（fasting plasma glucose,FPG）、空腹血胰岛素水平（fastingser Hmlevel of insulin,FINS）,并计算胰岛素抵抗指数（insulin resistance index,IRI）。结果：去势治疗6个月时,4组患者均有FINS的上升和IRI的升高．且IAB组较手术去势组更为明显（FINS：tA：B=7．7516、P〈0．01,tC：D=4．8078、P〈0．01;IRI：tA：B=7．3671、P〈0．01,tC：D=5．1005、P〈0．01）。在去势治疗12个月时,由于IAB进入治疗间歇期,D组FINS恢复到治疗前水平（q=2．5255,P〉0．05）;B组FINS较6个月时下降（q=9．0942,P〈0．01）;而手术去势组FINS及IRI未见下降。结论：去势治疗会促使晚期前列腺癌患者胰岛素抵抗的发生,但在IAB治疗间歇期,胰岛素抵抗逐渐恢复正常。     

Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) in BPH and PCa. ERβ agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNFα knock-out mice fail to respond to ERβ agonist, demonstrating the requirement for TNFα signaling. In human tissues, ERβ agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133⁺ enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ERβ causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ERβ agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ERβ agonist for treatment of PCa and/or BPH with or without androgen withdrawal.     

Progesterone as a morphological regulatory factor of the male and female gerbil prostate

Testosterone (T) and oestrogen are the main active steroid hormones in the male and female reproductive system respectively. In female rodents progesterone (P4), together with testosterone and oestrogen, has an essential role in the regulation of the oestrous cycle, which influences the prostate physiology through their oscillations. In this work we investigated how the male and female prostate gland of Mongolian gerbils responds to surgical castration at the start of puberty and what are the effects of T, oestradiol (E2) and P4 replacement, using both quantitative and qualitative methods. We also examined the location of the main steroid receptors present in the prostate. In the castrated animals of both sexes an intense glandular regression, along with disorganization of the stromal compartment, and abundant hyperplasia was observed. The replacement of P4 secured a mild recovery of the glandular morphology, inducing the growth of secretory cells and restoring the androgen receptor (AR) cells. The administration of P4 and E2 eliminated epithelial hyperplasia and intensified gland hypertrophy, favouring the emergence of prostatic intraepithelial neoplasia (PIN). In animals treated with T and P4, even though there are some inflammatory foci and other lesions, the prostate gland revealed morphology closer to that of control animals. In summary, through the administration of P4, we could demonstrate that this hormone has anabolic characteristics, promoting hyperplasia and hypertrophy, mainly in the epithelial compartment. When combined with E2 and T, there is an accentuation of glandular hypertrophy that interrupts the development of hyperplasia and ensures the presence of a less dysplastic glandular morphology.