Transforming growth factor-ß signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.

Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-ß acts on them are poorly understood. So, this study aims to identify whether or not TGF-ß acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-ß1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-ßR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-ßR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-ß1-treated ovaries. Western blot and morphological analyses indicated that TGF-ß signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-ß signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries.

Study on anti-tumor activities of ginsenoside structure modification HRG in vivo / 中国药学杂志

OBJECTIVE: To explore the anti-tumor activities of a new compound 3β,12β,20(S)-trihydroxy dammarane-3-O-β-D-glucopyranosyl (1-2)-β-D-glucopyranoside (HRG), which is a substance of ginsenoside structure modification, in vivo. METHODS: Liver cancer H22 tumor model on the chick chorioallantoic membrane (CAM) was established to observe the effects of HRG on tumor growth, the number of induced vessels and the growth inhibition rate. The implanted tumors were dyed by hematoxylin-eosin (HE), and the morphological properties were studied with light microscope. Immunohistochemistry (SP method) was used to detect the expressions of the implanted tumor's MVD and VEGF. RESULTS: HRG inhibited the tumor growth at 25, 50 and 100 μg · mL-1. Compared with the model control group, the inhibitory rates of the tumor growth were 27.73%, 50.02%, and 64.21%, respectively. HRG significantly reduced the number of tumor-induced vessels. At the same time, there existed different degree necrosis among the treatment groups, and the degree of necrosis had an inverse relationship with the number of tumor-induced vessels. In addition, HRG reduced the MVD of the implanted tumors, and decreased the expression of VEGF. CONCLUSION: HRG has good anti-tumor activities in vivo, and can significantly inhibit the growth of liver cancer H22-CAM tumor and the induction of angiogenesis. The mechanisms may be associated with lower tumor MVD and VEGF expression.