Objective The androgen signaling pathway is involved in the regulation of early follicular growth and follicular atresia, and sex hormone binding globulin (SHBG) is an important factor in regulating the level of local ovarian androgen.This study was to investigate the effects of androgen on the expression of SHBG in ovarian granulosa cells.Methods Human ovarian granule cancer cells were cultured with 0 nmol/L dihydrotestosterone (DHT), 500 nmol/L DHT, or 500 nmol/L DHT + 60 μmol/L Flutamide.The expression of SHBG was detected by Western blot and immunofluorescence staining.Hyperandrogenism (HA) was induced in 6 SD rats by subcutaneous injection of dehydroepiandrosterone (DHEA) and another 6 rats were included in the vehicle control group.At 35 days after modeling, all the rats were sacrificed for measurement of the level of SHBG in the blood from the inferior caval vein by ELISA, the expression of SHBG in the ovarian granulosa cells by immunohistochemistry, and expressions of androgen receptor (AR) and SHBG in the liver by Western blot.Results At 24 hours after modeling, the expression of AR was significantly upregulated in the 300, 400, and 500 nmol/L DHT groups as compared with the 0 nmol/L DHT group (1.06±0.02, 1.61±0.11, and 2.38±0.14 vs 1.06±0.03, P<0.05), and so was that of SHBG, increasing in a concentration-dependent manner, most significantly at 500 nmol/L (P<0.01).Both the expressions of AR and SHBG proteins remarkably elevated in the 500 nmol/L DHT group in comparison with the 0 nmol/L DHT group (P<0.01), but markedly downregulated as compared with the 500 nmol/L DHT + 60 μmol/L Flutamide group (P<0.05).Immunofluorescence staining showed that DHT promoted while the addition of Flutamide inhibited the expressions of AR and SHBG.Immunohistochemical staining of the ovarian tissue revealed a high level of SHBG in the HA rats.Compared with the control group, the HA animals exhibited a significantly decreased expression of serum SHBG (4.80±0.35 vs 2.41±0.14, P<0.01) and that in the liver, but a markedly increased level of the AR protein (P<0.05).Conclusion Activation of the androgen signaling pathway by DHT can promote the expression of SHBG in rat ovarian granulosa cells.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis