Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus.
Although estrogen has beneficial actions in brain, recent clinical trials demonstrated adverse neural effects of hormone therapy in postmenopausal women. The cause(s) of this disconnect between experimental and clinical findings may include unanticipated effects of progestins. We report that both natural progesterone and the clinical progestin medroxyprogesterone acetate block estrogen neuroprotection. These findings underscore the need to evaluate neural actions of progestins in the rational design of hormone therapy.
Rosario
Emily R
ER
Neuroscience Graduate Program, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, 90089-0191, USA.
Ramsden
Martin
M
Pike
Christian J
CJ
D000704:Analysis of Variance; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000293:injuries; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D010052:Ovariectomy; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D018690:Excitatory Amino Acid Agonists; D017258:Medroxyprogesterone Acetate; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid