Clinically Relevant Progestins Regulate Neurogenic and Neuroprotective Responses in Vitro and in Vivo

Previously, we demonstrated that progesterone (P4) promoted adult rat neural progenitor cell (rNPC) proliferation with concomitant regulation of cell-cycle gene expression via the P4 receptor membrane component/ERK pathway. Here, we report the efficacy of seven clinically relevant progestins alone or in combination with 17β-estradiol (E2) on adult rNPC proliferation and hippocampal cell viability in vitro and in vivo. In vitro analyses indicated that P4, norgestimate, Nestorone, norethynodrel, norethindrone, and levonorgestrel (LNG) significantly increased in rNPC proliferation, whereas norethindrone acetate was without effect, and medroxyprogesterone acetate (MPA) inhibited rNPC proliferation. Proliferative progestins in vitro were also neuroprotective. Acute in vivo exposure to P4 and Nestorone significantly increased proliferating cell nuclear antigen and cell division cycle 2 expression and total number of hippocampal 5-bromo-2-deoxyuridine (BrdU)-positive cells, whereas LNG and MPA were without effec...