Impact of progestins on estradiol potentiation of the glutamate calcium response.
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.
Nilsen
Jon
J
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.
Brinton
Roberta Diaz
RD
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
D004338:Drug Combinations; D018698:Glutamic Acid; D011374:Progesterone; D004958:Estradiol; D002118:Calcium