title: Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.
abstract: Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens.
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Jayaraman
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: cjpike@usc.edu.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Pike
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016912:Levonorgestrel / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D061251:Primary Cell Culture; D045167:Progesterone Congeners / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018696:Neuroprotective Agents; D045167:Progesterone Congeners; D004958:Estradiol; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate
keywords: BDNF; Neuroprotection; Oestrogen receptor; Progestagen