ReviewProgesterone and neuroprotection
Highlights
► Reviews the current state of knowledge on progesterone-induced neuroprotection. ► Reviews the receptor pharmacology associated with progesterone-induced protection. ► Reviews the signaling mechanisms that mediate progesterone-induced protection. ► Defines key differences in the neurobiology of progesterone and MPA.
Section snippets
The biology of progesterone
Progesterone, the natural progestin, is a major gonadal hormone that is synthesized primarily by the ovary in the female, and the testes and adrenal cortex in the male. While progesterone levels are generally higher in the female, it is worth noting that levels of progesterone during the female follicular phase of the menstrual cycle are similar to those seen in males (Strauss and Barbieri, 2004), and thus, may be equally important in males. The “classical” mechanism by which progesterone
Progesterone-induced neuroprotection
Progesterone has been reported to exert protective effects in a variety of experimental models that mimic certain pathogenic aspects of brain dysfunction seen with advanced age- or age-related neurodegenerative diseases such as Alzheimer's disease. For example, physiologically relevant concentrations of progesterone have been shown to significantly attenuate oxidative injury resulting from glutamate (Kaur et al., 2007, Nilsen and Brinton, 2002a, Nilsen and Brinton, 2002b, Nilsen and Brinton,
Mechanisms underlying progesterone's protective effects
Numerous mechanisms of action likely underlie the protective effects of progesterone. The classical genomic mechanism of progesterone action, for example, may be involved in the regulation of neurotrophin expression (Kaur et al., 2007), which in turn, could promote cell survival. Alternatively, progesterone may act through novel receptor systems, such as the membrane PR or the sigma receptor (another putative receptor for progesterone), to activate certain signal transduction pathways, which in
Progesterone and cognitive function
When considering the ovariectomized animal, it is important to recognize that this surgical intervention results in the loss of not just estradiol, but of progesterone as well. As such, the cognitive deficits we and others have observed following ovariectomy may have been contributed by the loss of circulating progesterone as well. And though numerous studies, including those from our laboratory, have clearly described the neuroprotective effects of progesterone against a wide array of insults
Receptor pharmacology of progesterone's protective effects
It is clear that the classical, intracellular/nuclear PR certainly plays an important role in mediating the effects of progesterone. For example, our laboratory has determined that the ability of progesterone to increase the expression (mRNA and protein levels) of brain-derived neurotrophic factor (BDNF), a key mediator of progesterone's protective effects, requires the classical PR (Jodhka et al., 2009). Further, Cai et al. (2008) have implicated the classical/intracellular PR in the
Why the type of progestin matters
It is estimated that by 2010, the population of women between the ages of 45 and 64 will reach approximately 42 million (U.S. Census Bureau. Projected population of the United States, by Age and Sex: 200 to 2050. www.census.gov/ipc/www/usinterimproj/ Internet release date: March 18, 2004). Among the health-related changes and decisions these women will need to consider include whether or not to consider the use of hormone therapy for not just the management of menopausal symptoms, but
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2022, Frontiers in NeuroendocrinologyHormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity
2022, Frontiers in NeuroendocrinologyCitation Excerpt :Reduced production, and thus, circulating levels of progesterone limits the ability of this hormone to carry out any dependent or interacting physiological processes (for recent review, Sundström-Poromaa et al., 2020). Progesterone action in the brain is highly complex, upregulating and downregulating various other neurotransmitter actions (serotonergic, dopaminergic, and GABAergic), interacting with other steroid hormones (Bäckström et al., 2011; Nguyen et al., 2017), and acting as a neuroprotective agent (Cai et al., 2008; Guennoun, 2020; Schumacher et al., 2016; Singh & Su, 2013). However, this latter class of effects is likely due to progesterone that is synthesized within the brain, independent of circulating concentrations (Micevych & Sinchak, 2008).
What is there to know about the effects of progestins on the human brain and cognition?
2022, Frontiers in NeuroendocrinologyThe association of reproductive stage with lobular cerebellar network connectivity across female adulthood
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