• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3083-3088
• /
• 2012

We investigated the prognostic value of pituitary tumor transforming gene 1 (PTTG1) expression according to clinicopathological features among localized or locally advanced prostate cancer cases receiving hormone therapy. A retrospective study involved 64 patients receiving combined androgen blockade treatment was performed. PTTG1 expression was determined by immunohistochemical staining using initial needle biopsy specimens for diagnosis. Associations of PTTG1 with various clinicopathological features and disease-free survival were examined via uni- and multivariate analyses. No association between PTTG1 expression and clinical T stage, Gleason score, pretreatment PSA levels, risk groups was found (p =0.682, 0.184, 0.487, 0.571, respectively). Univariate analysis revealed that increased PTTG1 expression, T3 stage and high risk group were associated with increased risk of disease progression (p =0.000, 0.042, and 0.001), and high PSA level had a tendency to predict disease progression (p =0.056). Cox hazard ratio analysis showed that PTTG1 low expression (p =0.002), PTTG1 high expression (p =0.000) and high risk group (p =0.0147) were significantly related to decreased disease-free survival. In conclusion, PTTG1 expression determined by immunohistochemical staining in needle biopsy specimens for diagnosis is a negative prognostic factor for progression in localized or locally advanced prostate cancer receiving hormone therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1033-1036
• /
• 2015

Background: Testosterone, a primary androgen in males, is converted into its most active form, dihydrotestosterone (DHT), by $5{\alpha}$-reductase type 2 (encoded by the SRD5A2 gene) in the prostate. DHT is necessary for prostatic growth and has five times higher binding affinity than testosterone for androgen receptors. We hypothesized that polymorphic variations in the SRD5A2 gene may affect the risk of benign prostatic hyperplasia and prostate cancer. Materials and Methods: We analyzed SRD5A2 gene polymorphisms in 217 BPH patients, 192 PCa cases, and 171 controls. Genotyping was undertaken using direct DNA sequencing. Genotype data were compared between cases and controls using a Chi square statistical tool. Results: We found that the A49T locus was monomorphic with 'AA' genotype in all subjects. At V89L locus, the presence of 'VV' showed a marginally significant correlation with increased BPH risk (p=0.047). At the $(TA)_n$ locus, longer TA repeats were found to be protective against BPH (p=0.003). However, neither of these polymoprhisms correlated with the risk of PCa. Conclusions: We conclude that A49T is monomorphic in the study population, VV marginally correlates with BPH risk, and longer $(TA)_n$ repeats are protective against BPH. None of these polymorphisms affect the risk of PCa.

• Development and Reproduction
• /
• v.15 no.1
• /
• pp.53-59
• /
• 2011

Sex steroid hormones are key molecules to prepare the decidual response and their levels are important in this process. Imbalances of the levels of steroid hormones are cause of implantation failure and other diseases including physical weakness. Androgen replacement therapy or selective androgen receptor modulator are used to overcome various diseases but long-term use may cause of side effects. In previous report, it is suggested that the steroid hormonal complexes derived from pig enhance the proliferation of satellite cell. Therefore, to evaluate the possible usage of steroid hormonal complex derived from pig testis (tS-C), the effects of tS-C on uterine response were studied using the model of artificial decidua. tS-C did not disturb the rhythmical estrus cycle. Artificial-induced decidual response was normally induced in tS-C administered mice. The histological characters of the decidua of tS-C administered mice were not different from the vehicle. The expression patterns of molecular markers of decidua were not different between vehicle and tS-C group. Collectively these results suggested that tS-C does not disturb the uterine responsibility to the embryo. In addition, our results suggested that tS-C can be applied to overcome the various problems such as loss of muscle mass and anemia.

• Annals of Clinical Neurophysiology
• /
• v.8 no.1
• /
• pp.63-70
• /
• 2006

Background: Testosterone is reported to have neuroprotective effect in various neurological diseases. Recently, the mechanism involved in nitric oxide (NO)-mediated motor neuron death is under extensive investigation. The Cu/Zn-superoxide dismutase (SOD1) mutations has been implicated in selective motor neuron death of amyotrophic lateral sclerosis (ALS) and it is said to play an important role in NO-mediated motor neuron death. However, neuroprotective effect of testosterone on motor neuron exposed to NO has rarely been studied. Methods: Motor neuron-neuroblastoma hybrid cells expressing wild-type or mutant (G93A or A4V) SOD gene were treated with $200{\mu}M$ S-nitrosoglutathione. After 24 hr, cell viability was measured by MTT assay. To see the neuroprotective effect of testosterone, pretreatment with 1 nM testosterone was done 1 hr before S-nitroglutathione treatment. To study the mechanism of protective effect, $20{\mu}M$ flutamide (androgen receptor antagonist) was also pretreated with testosterone 1 hr before S-nitroglutathione treatment. Results: S-nitrosoglutathione showed significant neurotoxic effect in all three cell lines. Percentage of cell death was somewhat different in each cell line. 1 nM testosterone showed neuroprotective effect in G93A and wild-type cell line. In A4V cell line, testosterone did not showed neuroprotective effect. The neuroprotective effect of testosterone was reversed by $20{\mu}M$ flutamide. Conclusions: These results indicate that testosterone induces neuroprotection in NO-mediated motor neuron death directly through the androgen receptor. This neuroprotective effect of testosterone varies according to the types of SOD1 gene mutation. These data suggest that testosterone may be of therapeutic value against ALS.

• Development and Reproduction
• /
• v.19 no.2
• /
• pp.69-77
• /
• 2015

Cell-cell direct communication through channel-forming molecules, connexin (Cx), is essential for a tissue to exchange signaling molecules between neighboring cells and establish unique functional characteristics during postnatal development. The corpus epididymis is a well-known androgen-responsive tissue and involves in proper sperm maturation. In the present research, it was attempted to determine if expression of Cx isoforms in the corpus epididymis in the adult is modulated by exposure to estrogenic or anti-androgenic compound during the early postnatal period. The neonatal male rats at 7 days of age were subcutaneously injected by estradiol benzoate (EB) at low-dose ($0.015{\mu}g/kg$ body weight) or high-dose ($1.5{\mu}g/kg$ body weight) or flutamide (Flu) at low-dose ($500{\mu}g/kg$ body weight) or high-dose (50 mg/kg body weight). The corpus epididymis collected at 4 months of age was subjected to evaluate expressional changes of Cx isoforms by quantitative real-time PCR. Treatment of low-dose EB resulted in increases of Cx32, Cx37, and Cx45 transcript levels, while exposure to high-dose EB decreased expression of Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45. Treatments of Flu caused significant decreases of expression of all examined Cx isoforms, except Cx37 and Cx43 shown no expressional change with high-dose Flu treatment. These findings imply that expression of most Cx isoforms present in the corpus epididymis would be transcriptionally regulated by actions of androgen and/or estrogen during postnatal period.

• Development and Reproduction
• /
• v.16 no.1
• /
• pp.53-58
• /
• 2012

Circadian rhythmicity (e.g. secretory pattern of hormones) plays an important role in the control of reproductive function. We hypothesized that the alteration of feeding pattern via meal time shift/restriction might disrupt circadian rhythms in energy balance, and induce changes in reproductive activities. To test this hypothesis, we employed simple animal model that not allowing $ad$ $libitum$ feeding but daytime only feeding. The animals of $ad$ $libitum$ feeding group (Control) have free access to food for 4 weeks. The day feeding (=reverse feeding, RF) animals (RF group) have restricted access to food during daytime (0900-1800) for 4 weeks. After completing the feeding schedules, body weights, testis and epididymis weights of animals from both group were not significantly different. However, the weights of seminal vesicle (control : RF group = $0.233{\pm}0.014g$ : $0.188{\pm}0.009g$, $p$<0.01) and prostate (control : RF group = $0.358{\pm}0.015g$ : $0.259{\pm}0.015g$, $p$<0.001) were significantly lower in RF group animals. The mRNA levels of pituitary common alpha subunit ($C{\alpha}$; control : RF group = $1.0{\pm}0.0699$ AU : $0.1923{\pm}0.0270$ AU, $p$<0.001) and $FSH{\beta}$ (control : RF group = $1.0{\pm}0.1489$ AU : $0.5237{\pm}0.1088$ AU, $p$<0.05) were significantly decreased in RF group. The mRNA levels of ACTH were not significantly different. We were unable to find any prominent difference in the microstructures of epididymis, and there were slight alterations in those of seminal vesicles after 4 weeks of reversed feeding when compared to control samples. The present study demonstrates that the shift and/or restriction of feeding time could alter the pituitary gonadotropin expression and the weights of seminal vesicle and prostate in rats. These data suggest the lowered gonadotropin inputs may decrease androgen secretion form testis, and consequently results in poor response of androgen-dependent tissues such as seminal vesicle and prostate.

• Journal of Life Science
• /
• v.21 no.4
• /
• pp.481-485
• /
• 2011

T0901317 is a potent synthetic ligand for liver X receptor (LXR, NR1H2/3), a member of the nuclear receptor superfamily that functions as a transcription factor. However, T0901317 has been also reported to modulate the activity at least four other nuclear receptors (NRs), acting as agonists for farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2) and as antagonists for androgen receptor (AR, NR3C4) and retinoid-related orphan receptor-${\alpha}$ (ROR-${\alpha}$, NR1F1). We report here that T0901317 can also function as an inhibitor for constitutive androstane receptor (CAR, NR1I3). Since CAR is a major player of xenobiotic and cholesterol metabolism in the liver, along with PXR, FXR and LXR, which are reported to be regulated by T0901317, this further complicates the interpretation of potential results with T0901317 in liver cells.

• Korean Journal of Food Science and Technology
• /
• v.46 no.4
• /
• pp.516-521
• /
• 2014

The mechanisms underlying the refractory effects of flutamide, a first-line oral anti-androgen drug, have not been entirely elucidated. In the present study, we investigated the mechanism of flutamide-induced hormone-refractory prostate cancer cell growth and its modulation by resveratrol, a phytoalexin present in grapes. Resveratrol significantly attenuated interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) transcriptional activity and dihydrotestosterone (DHT) or IL-6-induced prostate-specific antigen (PSA) transcriptional activity. Furthermore, compared to treatment with DHT or IL-6 alone, combination treatment of cells significantly increased PSA transcriptional activity, and resveratrol markedly diminished DHT plus IL-6-induced STAT3 and PSA transcriptional activities. Thus, the inhibitory effects of resveratrol on IL-6-, DHT-, and flutamide-induced hormone-refractory prostate cancer cell growth are partly mediated by the suppression of STAT3 reporter gene activity, suggesting that resveratrol represents a promising therapy for prostate cancer.

• Journal of the Korea Institute of Information and Communication Engineering
• /
• v.18 no.2
• /
• pp.482-487
• /
• 2014

This study is to investigate the effects of testosterone on adipogenesis and its molecular mechanism using RT-PCR analysis and transient transfection assays. Castrated(CAST) mice treated with testosterone had lower white adipose tissue weights and expression of adipocyte-specific genes($PPAR{\gamma}$ and aP2) than CAST control mice. Consistent with the in vivo data, testosterone treatment inhibited triglyceride accumulation and expression of adipocyte-specific genes($PPAR{\gamma}$ and aP2) in differentiated 3T3-L1 cells compared with control group. Testosterone-activated androgen receptor(AR) repressed the luciferase reporter gene activity induced by $PPAR{\gamma}$ transfection. Thus, these results suggest that testosterone downregulates the actions of $PPAR{\gamma}$ on adipogenesis through AR.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.6
• /
• pp.1561-1566
• /
• 2006

Sebum is secreted due to the effect of androgen, which start to be secreted at puberty. Androgens have profound effects on the physiology of the sebaceous gland, Using the human sebocyte cell line SZ95, we investigated the inhibitory effect of Chelidonii Harba (CH) on the subum production. Our results showed that numerous cytoplasmic lipid droplets were examined by Oil red staining and lipid droplets were increased markedly by testosterone. Cell viability was dose-dependently decreased by CH as compared with untreated cells, while total lipid content and cholesterol slightly were increased by CH. Testosterone significantly stimulated the synthesis of total lipid and the synthesis of specific sebaceous lipids such as cholesterol and triglyceride. Combined treatment with CH and testosterone resulted in a lower lipid synthesis than with testosterone alone. Especially cholesteol content was reduced by combined treatment with CH and testosterone. These results indicate that CH inhibits the testosterone-induced lipid synthesis in SZ95 cells and acts antagonistically to androgen at the cellular level.