OBJECTIVETo investigate the antiandrogenic activities of cypermethrin and beta-cypermethrin in vitro and in vivo.

METHODSTranscriptional activation assay based on MDA-kb2 cell was used to determine the antiandrogenic effect of cypermethrin and beta-cypermethrin in vitro. The cells were treated by 10(-8), 10(-7), 10(-6) and 10(-5) mol/L of cypermethrin and beta-cypermethrin with 1.0 nmol/L DHT at the same time. The effects of antagonism towards the androgenic receptor were studied. In in vivo assays, Hershberger assay was used to determine the antiandrogenic activities of cypermethrin and beta-cypermethrin. Six-week-old castrated male SD rats were administered by cypermethrin (7, 21 and 63 mg/kg) and beta-cypermethrin (6, 18 and 54 mg/kg). After 7-day treatments, all rats were euthanized and androgen-responsive tissues were excised and weighed respectively.

RESULTSThe in vitro experiments showed that 10(-6) and 10(-5) mol/L cypermethrin could inhibit significantly the antagonism activity towards the androgenic receptor of DHT. In in vivo tests, the weight of seminal vesicle, ventral prostate, dorsolateral prostate and preputial glands in the 63 mg/kg cypermethrin [(52.8 +/- 7.1), (42.4 +/- 8.9), (36.6 +/- 4.5) and (43.4 +/- 11.1) mg] decreased significantly compared with those in the control group. In 21 mg/kg cypermethrin treated group only the weights of ventral prostate and dorsolateral prostate decreased significantly, and in 7 mg/kg cypermethrin only the weight of dorsolateral prostate decreased (P < 0.05). For beta-cypermethrin, any antiandrogen effect in in vivo and in vitro experiments was not found in all the groups.

CONCLUSIONCypermethrin is a moderate antiandrogen that elicits antiandrogenic effects at least partly by antagonizing AR and beta-cypermethrin is not an antiandrogen in our experiments.

Androgen Antagonists ; pharmacology ; Animals ; Cells, Cultured ; Male ; Organ Size ; Prostate ; drug effects ; Pyrethrins ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen ; drug effects ; Seminal Vesicles ; drug effects

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.
Androgen Antagonists/therapeutic use* ; Androgen Receptor Antagonists/therapeutic use* ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Prostatic Neoplasms/genetics* ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Receptors, Androgen/drug effects*

AIMTo study the effect of curcumin on the apoptosis of prostate cancer cell line LNCaP and regulation of expression of maspin gene.

METHODSMTT and DNA electrophoresis were used to examine the cell growth and apoptosis of prostate cancer cell line LNCaP after treated with different doses of curcumin. The expression of maspin gene at transcription level and translation level was also detected by RT-PCR and Western blotting. pGL3-maspin luciferase expression vector, containing 847 bp (- 764 -/+ 83) DNA of maspin gene 5' promoter region, was transient transfected into LNCaP cell. Through detecting the activity of luciferase, the effect of curcumin on the promoter of maspin was studied.

RESULTSCurcumin inhibited cell growth, induced the apoptosis and enhanced the expression of maspin gene in LNCaP cells.

CONCLUSIONCurcumin up-regulated expression of maspin gene in LNCaP cells through enhancing the transcription activity of promoter of maspin gene.

Androgen Receptor Antagonists ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Male ; Promoter Regions, Genetic ; Prostatic Neoplasms ; drug therapy ; genetics ; pathology ; RNA, Messenger ; analysis ; Receptors, Androgen ; genetics ; Serpins ; genetics

The effects of androgen on lipid and the cardiovascular system are very important. The relationship between androgen and lipoprotein is rather complicated and influenced by many factors. The effects of endogenous androgen on the metabolism of lipoprotein vary with age, environment, nutrition and gender, while the effects of exogenous androgen on lipoprotein vary with different androgen preparations, administration methods and diseases to be treated. Androgen can impact the metabolism of lipoprotein, vascular endothelium, macrophage, vascular smooth muscle, angiotasis, blood coagulation, platelet and so on. The effects of polymorphism of the androgen receptor gene CAG on the cardiovascular system are important and yet somehow controversial and have to be further investigated.
Androgens ; pharmacology ; physiology ; Cardiovascular System ; drug effects ; Female ; Humans ; Lipoproteins ; metabolism ; Male ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; physiology

OBJECTIVE: To investigate androgen receptor (AR) expression and the effect of epidermal growth factor (EGF) and testosterone on AR expression level.
 METHODS: EGF or different concentrations of testosterone were incubated with the primary urethral plate fibroblasts from patients with hypospadias. The levels of AR expression in the fibroblasts were detected by immunocytochemical assays and graphical analysis.
 RESULTS: There was no significant difference in AR activation under physiological concentrations (3×10(-8) mol/L) of testosterone between the control and the distal hypospadias group (P>0.05). However, there was a significant decrease in AR activation in the proximal hypospadias group compared to that in the control group (P<0.001). Under the concentration of 3×10(-6) mol/L, the effects of testosterone on AR activation were dramatically different in the three groups (control group>distal hypospadias group>proximal hypospadias group, P<0.001). AR activation level in the group of proximal hypospadias was improved most obviously when EGF and physiological concentration of testosterone were employed in the urethral plate fibroblasts from hypospadias patients (P<0.001), and it was improved more in the distal hypospadias group than that in the control group (P=0.02).
 CONCLUSION AR expression and activation in the urethral plate fibroblasts from hypospadias patients are abnormal. EGF can be used to improve AR activation in fibroblasts from different types of hypospadias, especially in the proximal type.
Cells, Cultured ; EGF Family of Proteins ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Humans ; Hypospadias ; metabolism ; Male ; Receptors, Androgen ; metabolism ; Testosterone ; pharmacology

The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.
Antineoplastic Agents, Phytogenic/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Receptors, Androgen/drug effects* ; Signal Transduction/drug effects* ; Taxoids/therapeutic use*

BACKGROUNDThe failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR). Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone. This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17beta-estradiol, and progesterone, respectively.

METHODSLNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17beta-estradiol, and progesterone, respectively.

RESULTSGrowth of LNCaPas-AR was inhibited significantly (P < 0.05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L 17beta-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen between LNCaP and LNCaPNeo (P > 0.05). Microscopic observation showed that LNCaP and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive.

CONCLUSIONSOur observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer.

Androgen Receptor Antagonists ; Cell Division ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Estradiol ; pharmacology ; Humans ; Male ; Metribolone ; antagonists & inhibitors ; pharmacology ; Progesterone ; antagonists & inhibitors ; pharmacology ; Prostatic Neoplasms ; pathology ; therapy ; RNA, Antisense ; therapeutic use ; Receptors, Androgen ; genetics

PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over time.
Animals ; Apoptosis/drug effects ; Cell Proliferation ; Embryonic Development/*drug effects ; Environmental Pollutants/*toxicity ; Female ; Male ; *Maternal Exposure ; Mice ; Mice, Inbred C57BL ; Organ Size/drug effects ; Pregnancy ; Receptors, Androgen/metabolism ; Testis/*drug effects/embryology/pathology ; Tetrachlorodibenzodioxin/*toxicity

OBJECTIVETo investigate the effects of testosterone on the proliferation of penile corpus cavernosal cells in male SD rats.

METHODSSmooth muscle cells (SMCs) and fibroblasts collected from the corpus cavernosal tissues of male SD rats were cultured by the enzymatic dispersion method and detected for the expression of the androgen receptor (AR) by immunohistochemistry. The effects of testosterone on the SMCs and fibroblasts were observed by methyl thiazolyl tetrazolium (MTT) assay in different concentration groups (10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, 10(-4) mol/L and 10(-3) mol/L) in comparison with the control.

RESULTSThe AR expression was found in the penile corpus cavernosal tissues. MTT assay showed that, at the concentration of 10(-5) mol/L, testosterone induced the proliferation of SMCs (68100 +/- 2200) and fibroblasts (70200 +/- 1300), with significant differences from the control ( P < 0.05), while at 10(-4) mol/L, it inhibited their proliferation (55000 +/- 1400 and 59100 +/- 1500, respectively), (P < 0.01). No significant effects were noted in the other concentration groups.

CONCLUSIONAR exists in the penile corpus cavernosal tissues of male rats. Testosterone modulates the proliferation of corpus cavernosum tissue cells through AR, and different concentrations of testosterone may be positively or negatively correlated with the proliferation of SMCs and fibroblasts.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Fibroblasts ; cytology ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Penis ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen ; metabolism ; Testosterone ; pharmacology

OBJECTIVETo study the inhibitory effect of matrine on the proliferation of the prostate cancer cell line LNCaP and the expression of the androgen receptor (AR).

METHODSLNCaP cells were treated with matrine at the concentration of 0.5, 1.0, 1.5, 2.0 and 3.0 g/L for 12, 24 and 36 hours, the cell growth activity determined by MTT colorimetry and trypan blue staining at 36 hours, the cell cycle changes detected by flow cytometry and the expression of AR by Western blot at 24 hours.

RESULTSMatrine suppressed the in vitro growth of the androgen-sensitive prostate cancer cell line LNCaP in a time- and dose-dependent manner, blocked the cell cycles in the G2/M phase and decreased the expression of AR in the cell line in a dose-dependent manner (P < 0.01).

CONCLUSIONMatrine can significantly inhibit the in vitro growth of NCaP cells by down-regulating the expression of AR and blocking cell cycles.

Alkaloids ; pharmacology ; Blotting, Western ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Flow Cytometry ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Quinolizines ; pharmacology ; Receptors, Androgen ; metabolism