Abstract
Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair.
Highlights
Over the past two decades, the pleiotropic effects which steroids exert throughout the nervous system have become an active area of investigation in neuroendocrine science
In oligodendrocytes, the conversion of progesterone to 5α-DHP by the type 1 isoform of the 5α-reductase was highest. These results indicate that adult oligodendrocytes actively metabolize progesterone derived from the circulation or other neural cells to 5α-DHP, which may play a role in the regulation of oligodendroglial functions and in the maintenance of myelin
Increased levels of progesterone and 3βhydroxysteroid dehydrogenase (3β-HSD) expression were observed within the brains of dysmyelinating jimpy and shiverer mouse mutants (Le Goascogne et al, 2000). These findings strongly suggest that increased progesterone synthesis in the central nervous system (CNS) may be part of endogenous neuroprotective mechanisms and may correspond to a physiological response of neural cells to injury and degenerative conditions (De Nicola et al, 2009)
Summary
Over the past two decades, the pleiotropic effects which steroids exert throughout the nervous system have become an active area of investigation in neuroendocrine science. Since the pioneering studies of the biosynthesis, mechanisms of action, and effects of steroids in the brain in the late 1980s and early 1990s, extensive investigations have improved our knowledge in this field. Estradiol was shown to have marked influences on synaptic and dendritic spine plasticity (Gould et al, 1990; McEwen, 2001). Neuroprotective effects of both progestagens and estrogens were demonstrated in different experimental models of nervous system injury, ranging from middle cerebral artery occlusion (MCAO), excitotoxic neuron death, and traumatic brain injury (TBI) to spinal cord lesions (Garcia-Segura et al, 2001; Stein, 2001; Wise, 2002; De Nicola et al, 2009). Soon after the discovery that some steroids, and in particular pregnenolone and progesterone, can be synthesized de novo from cholesterol within the nervous system, these so-called “neurosteroids” were proposed to play a role in myelination
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
