Show simple item record

dc.contributor.authorLiu, Lifei
dc.contributor.authorZhao, Liqin
dc.contributor.authorShe, Hongyun
dc.contributor.authorChen, Shuhua
dc.contributor.authorWang, Junming
dc.contributor.authorWong, Charisse
dc.contributor.authorMcClure, Kelsey
dc.contributor.authorSitruk-Ware, Regine
dc.contributor.authorBrinton, Roberta Diaz
dc.date.accessioned2015-05-13T17:24:52Z
dc.date.available2015-05-13T17:24:52Z
dc.date.issued2010
dc.identifier.citationLiu et al. "Clinically Relevant Progestins Regulate Neurogenic and Neuroprotective Responses in Vitro and in Vivo." Endocrinology, December 2010, 151(12):5782–5794.

http://dx.doi.org/10.1210/en.2010-0005
en_US
dc.identifier.urihttp://hdl.handle.net/1808/17752
dc.description.abstractPreviously, 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 effect. Mechanistically, neurogenic progestins required activation of MAPK to promote proliferation. P4, Nestorone, and LNG significantly increased ATP synthase subunit α (complex V, subunit α) expression, whereas MPA was without effect. In combination with E2, P4, Nestorone, LNG, and MPA significantly increased BrdU incorporation. However, BrdU incorporation induced by E2 plus LNG or MPA was paralleled by a significant increase in apoptosis. A rise in Bax/Bcl-2 ratio paralleled apoptosis induced by LNG and MPA. With the exception of P4, clinical progestins antagonized E2-induced rise in complex V, subunit α. These preclinical translational findings indicate that the neurogenic response to clinical progestins varies dramatically. Progestin impact on the regenerative capacity of the brain has clinical implications for contraceptive and hormone therapy formulations prescribed for pre- and postmenopausal women.

Clinical progestins vary dramatically in their impact on the regenerative capacity of the brain and thus are likely to have clinical implications for long-term neurological function.
en_US
dc.description.sponsorshipThis work was supported by National Institute on Aging Grant 1 PO1 AG026572, Project 3 of Progesterone in Brain Aging and Alzheimer’s Disease Program Project (to R.D.B.)en_US
dc.publisherEndocrine Societyen_US
dc.titleClinically Relevant Progestins Regulate Neurogenic and Neuroprotective Responses in Vitro and in Vivoen_US
dc.typeArticle
kusw.kuauthorZhao, Liqin
kusw.kudepartmentDepartment of Pharmaceutical Chemistryen_US
dc.identifier.doi10.1210/en.2010-0005
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record