Progesterone and neuroprotection
- PMID: 22732134
- PMCID: PMC3467329
- DOI: 10.1016/j.yhbeh.2012.06.003
Progesterone and neuroprotection
Abstract
Numerous studies aimed at identifying the role of estrogen on the brain have used the ovariectomized rodent as the experimental model. And while estrogen intervention in these animals has, at least partially, restored cholinergic, neurotrophin and cognitive deficits seen in the ovariectomized animal, it is worth considering that the removal of the ovaries results in the loss of not only circulating estrogen but of circulating progesterone as well. As such, the various deficits associated with ovariectomy may be attributed to the loss of progesterone as well. Similarly, one must also consider the fact that the human menopause results in the precipitous decline of not just circulating estrogens, but in circulating progesterone as well and as such, the increased risk for diseases such as Alzheimer's disease during the postmenopausal period could also be contributed by this loss of progesterone. In fact, progesterone has been shown to exert neuroprotective effects, both in cell models, animal models and in humans. Here, we review the evidence that supports the neuroprotective effects of progesterone and discuss the various mechanisms that are thought to mediate these protective effects. We also discuss the receptor pharmacology of progesterone's neuroprotective effects and present a conceptual model of progesterone action that supports the complementary effects of membrane-associated and classical intracellular progesterone receptors. In addition, we discuss fundamental differences in the neurobiology of progesterone and the clinically used, synthetic progestin, medroxyprogesterone acetate that may offer an explanation for the negative findings of the combined estrogen/progestin arm of the Women's Health Initiative-Memory Study (WHIMS) and suggest that the type of progestin used may dictate the outcome of either pre-clinical or clinical studies that addresses brain function.
Copyright © 2012 Elsevier Inc. All rights reserved.
Similar articles
-
Mechanisms of progesterone-induced neuroprotection.Ann N Y Acad Sci. 2005 Jun;1052:145-51. doi: 10.1196/annals.1347.010. Ann N Y Acad Sci. 2005. PMID: 16024757 Review.
-
Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.JAMA. 2003 May 28;289(20):2663-72. doi: 10.1001/jama.289.20.2663. JAMA. 2003. PMID: 12771113 Clinical Trial.
-
Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.JAMA. 2003 May 28;289(20):2651-62. doi: 10.1001/jama.289.20.2651. JAMA. 2003. PMID: 12771112 Clinical Trial.
-
Progestins and neuroprotection: are all progestins created equal?Minerva Endocrinol. 2007 Jun;32(2):95-102. Minerva Endocrinol. 2007. PMID: 17557035 Review.
-
Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy.Brain Res. 2013 Jun 13;1514:98-106. doi: 10.1016/j.brainres.2013.01.027. Epub 2013 Jan 20. Brain Res. 2013. PMID: 23340161 Free PMC article. Review.
Cited by
-
CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.Sci Rep. 2024 Apr 4;14(1):7922. doi: 10.1038/s41598-024-58104-9. Sci Rep. 2024. PMID: 38575662 Free PMC article.
-
Exploring sex differences: insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology.Front Neurosci. 2024 Feb 21;18:1340108. doi: 10.3389/fnins.2024.1340108. eCollection 2024. Front Neurosci. 2024. PMID: 38449735 Free PMC article. Review.
-
Understanding the Biological Relationship between Migraine and Depression.Biomolecules. 2024 Jan 30;14(2):163. doi: 10.3390/biom14020163. Biomolecules. 2024. PMID: 38397400 Free PMC article. Review.
-
Animal Approaches to Studying Risk Factors for Parkinson's Disease: A Narrative Review.Brain Sci. 2024 Feb 2;14(2):156. doi: 10.3390/brainsci14020156. Brain Sci. 2024. PMID: 38391730 Free PMC article. Review.
-
Depression in Women: Potential Biological and Sociocultural Factors Driving the Sex Effect.Neuropsychobiology. 2024;83(1):2-16. doi: 10.1159/000531588. Epub 2024 Jan 25. Neuropsychobiology. 2024. PMID: 38272005 Free PMC article. Review.
References
-
- Adams MR, Register TC, Golden DL, Wagner JD, Williams JK. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Arterioscler Thromb Vasc Biol. 1997;17:217–221. - PubMed
-
- Attella MJ, Nattinville A, Stein DG. Hormonal state affects recovery from frontal cortex lesions in adult female rats. Behav Neural Biol. 1987;48:352–367. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials