This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning ...This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.展开更多
乳腺癌是导致女性死亡的主要病因之一,因此现在对于相关标志物及治疗靶位点的研究非常重要。妇女健康启动项目(Women’s Health Initiative,WHI)研究10年随访结果,单一雌激素治疗组妇女的乳腺癌风险没有增加,反而有降低,雌孕激素联合治...乳腺癌是导致女性死亡的主要病因之一,因此现在对于相关标志物及治疗靶位点的研究非常重要。妇女健康启动项目(Women’s Health Initiative,WHI)研究10年随访结果,单一雌激素治疗组妇女的乳腺癌风险没有增加,反而有降低,雌孕激素联合治疗组乳腺癌风险增高。此结果表明,在激素替代治疗(hormone replacement therapy,HRT)中孕激素对乳腺癌风险具有负面影响,许多体外研究发现某些合成孕激素对孕激素受体膜组分1(progesterone receptor membrane components,PGRMC1)表达阳性的人乳腺癌细胞有明显促增生作用。那么,WHI雌孕激素连续联合治疗组乳腺癌风险的增加是否可以用PGRMC1来解释?是否PGRMC1可以作为HRT乳腺癌易感者的潜在标志物?现就此方面的研究进行综述。展开更多
文摘This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.
