Effects of PE on estrogen receptor expressions and its transcriptional activation on target genes / 中国药理学通报

Aim To investigate the effect of piperazinyl estrone(PE) on estrogen receptor expression and the transcriptional regulation of target genes.Methods Ovariectomized mice were given with PE in different doses (0.5 mg·kg~(-1),1 mg·kg~(-1),2 mg·kg~(-1))and estrone(0.71 mg·kg~(-1)) for 42 days,the protein expressions of Ers(Erαand Erβ)were shown by immunohistochemical method; To study transcriptional regulation of PE, PACT2-hERα and ERE2-TATA-LUC were co-transfected into MCF-7 cells by using Tfx 50 cationic liposome.Results Compared with ovx group, the groups with PE could up-regulate Ers of uteri in a dose-dependent manner,but its effect on Erα subtype was obvious.The classical ER signaling pathways could be activated by PE in co-transfected MCF-7 cells,but activation of PE was feebler than estrone with the same dose.Conclusion PE can up-regulate estrogen receptors in uteri. PE can transactivate ERE reportor gene through Erα and Erβ in MCF-7 cells, but its effect is feeble.

Synthesis of 1,6-bis(L-alpha, beta-diaminopropionic acid) oxytocin / 生物医学工程学杂志

A novel derivative of oxytocin containing nonprotein amino acid L-alpha, beta-diaminopropionic acid (L-Dap) was synthesized by 7+2 fragment combination in solution. N beta of all the amino acid necessary was protected by carbobenzoxy (Z) and N beta of L-Dap was protected by tert. -butoxycarbonyl (Boc) . The important intermediate, heptapeptide, was synthesized by the stepwise elongation method using carbobenzoxy amino acid p-nitrophenyl esters in solution. Azide synthesis was used to get the nonapeptide. Z group was removed by treatment with 5% Pd/C and Boc with CF3COOH. Eight new compounds incorporating L-Dap were obtained and confirmed by the amino acid analysis and mass spectral detection.

Piperazinyl estrone, a new estrogen derivant, prevents bone loss in aged rats / 生物医学工程学杂志

The purpose of this study was to determine the effects of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uterine weight in female aged rats. Thirty-two Sprague-Dawley female rats at the age of 22 months were treated with vehicle or with piperazinyl estrone (P-E) at 0.5, 1 and 2 mg/kg/day, subcutaneous injection for 1 month. At the time of death, the uterine weight was measured and bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections. Compared with control, bone mass was increased in P-E groups. Dynamic data showed that bone resorption were decreased, but bone formation was not declined and bone mass was increased significantly in P-E (1 mg/kg day) group. There was no significant change in uterine weight. The findings of this study show that piperazinyl estrone at dosage of 1 mg/kg/d is most efficacious in preventing the bone losses in aged rats and has no side effect on uterus.

Regulation of XW630 on estrogen receptor messenger RNA expression in osteoblasts / 生物医学工程学杂志

This study was performed to investigate the mechanism of an anti-osteoporosis new drug XW630 for promoting the osteogenic action. Osteoblast clone was cultivated from SD adult rat calvaria in vitro, the estrogen receptor messenger RNA(ERmRNA) expression in the osteoblasts of rats was detected directly with high-sensitive RT-PCR firstly. The results indicated that XW630 can significantly promote ERmRNA expression in osteoblasts in the time-dependent manner. Being superior to other two kinds of estrogen in the same concentration (10(-6) mol/L), XW630 probably plays an important role in the bone pathogenesis by means of ER gene regulatory functions.

The synthesis and preliminary bioactivity of isoflavone derivatives / 第三军医大学学报

Objective To synthesize soybean isoflavones, and their 7-alkaline analogues and to evaluate their uterotrophic activities and anti-uterotrophic activities preliminarily. Methods The target molecules were synthesized by multi-step from resorcinol and p-substituted phenylacetic acid as the starting material. Their uterotrophic activities and anti-uterotrophic activities were evaluated by female mouse at the concentration of 1.1?10 -2 ?mol/ml and 1.85?10 -3 ?mol/ml. Results Twenty-two compounds were synthesized, among which 4 intermediates and 12 isoflavones are new compounds. Conclusion All the target molecules except for 6a show weak uterotrophic activities and high anti-uterotrophic activities.

Study of XW630 in promoting estrogen receptor expression in ovariectomized rats / 生物医学工程学杂志

We adopted firstly the dextran-coated charcoal(DCC) and SP methods to detect estrogen receptor (ER) expression of bone tissue in ovariectomized(OVX) rats. The results demonstrate that in OVX rats, XW630 can significantly promote ER expression in bone tissue and increase the ER content. XW630 is superior to estrone in effectiveness. The results also reveal that the ER expression in OVX rat bone tissue decreases with the lapse of time, indicating that the expression of ER depends on the existence of estrogen.