title: Impact of progestins on estradiol potentiation of the glutamate calcium response.
abstract: One mechanism by which estrogen may modulate cognitive function is through potentiation of glutamate-mediated rises in intracellular calcium ([Ca2+]i) with resultant effects on neuronal morphology and signaling. Since progesterone is a component of hormone replacement therapy (HRT), we sought to determine whether therapeutically relevant progestins attenuated or blocked estrogen potentiation of glutamate-induced [Ca2+]i rises. 17beta-estradiol and progesterone, alone or in combination, significantly potentiated the rise in [Ca2+]i. When co-administered, progesterone attenuated the estrogen response to the level seen with progesterone alone. In contrast, medroxyprogesterone acetate (MPA) had no effect when administered alone and completely blocked the 17beta-estradiol-induced potentiation when co-administered. These results may have important implications for effective use of HRT to maintain cognitive function during menopause and aging.
authors: Department of Molecular Pharmacology and Toxicology and the Program in Neuroscience, University of Southern California, Pharmaceutical Sciences Center, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors: Jon
authors: J
authors: Nilsen
authors: Roberta Diaz
authors: RD
authors: Brinton
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020249:Hormone Replacement Therapy; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004338:Drug Combinations; D018698:Glutamic Acid; D011374:Progesterone; D004958:Estradiol; D002118:Calcium