title: Progesterone promotes the survival of newborn neurons in the dentate gyrus of adult male mice.
abstract: 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 0-2nd day after the first BrdU-injection (BrdU-D(0-2)) 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-D(5-7), but not at BrdU-D(10-12) and BrdU-D(15-17). Androstenedione (Ad), testosterone (TE), or estradiol (E2) at the same-dose of P4, when administered at BrdU-D(0-2), could not replicate the effect of P4, while the inhibition of 5alpha-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.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Jiangsu, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D018696:Neuroprotective Agents; D015735:Mifepristone; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D001973:Bromodeoxyuridine