Progesterone Actions During Central Nervous System Development

González-Orozco, Juan Carlos; Camacho‐Arroyo, Ignacio

doi:10.3389/fnins.2019.00503

Cited by 72 publications

(45 citation statements)

References 140 publications

(195 reference statements)

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“…Progesterone has a broad spectrum of actions in the brain including reproduction and sexual behavior [ 101 , 102 ], CNS development and differentiation [ 103 , 104 ], myelination [ 105 ], and neuroprotection. In this review, we focus on the neuroprotective effects.…”

Section: Progesterone and Its Metabolites For Brain Neuroprotectiomentioning

confidence: 99%

Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

Guennoun

2020

IJMS

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Progesterone has a broad spectrum of actions in the brain. Among these, the neuroprotective effects are well documented. Progesterone neural effects are mediated by multiple signaling pathways involving binding to specific receptors (intracellular progesterone receptors (PR); membrane-associated progesterone receptor membrane component 1 (PGRMC1); and membrane progesterone receptors (mPRs)) and local bioconversion to 3α,5α-tetrahydroprogesterone (3α,5α-THPROG), which modulates GABAA receptors. This brief review aims to give an overview of the synthesis, metabolism, neuroprotective effects, and mechanism of action of progesterone in the rodent and human brain. First, we succinctly describe the biosynthetic pathways and the expression of enzymes and receptors of progesterone; as well as the changes observed after brain injuries and in neurological diseases. Then, we summarize current data on the differential fluctuations in brain levels of progesterone and its neuroactive metabolites according to sex, age, and neuropathological conditions. The third part is devoted to the neuroprotective effects of progesterone and 3α,5α-THPROG in different experimental models, with a focus on traumatic brain injury and stroke. Finally, we highlight the key role of the classical progesterone receptors (PR) in mediating the neuroprotective effects of progesterone after stroke.

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Section: Progesterone and Its Metabolites For Brain Neuroprotectiomentioning

confidence: 99%

Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

Guennoun

2020

IJMS

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“…In fact, because it is synthesized in the CNS of both males and females, it is referred as a neurosteroid and regulates several neural functions including neuroprotection, neuromodulation, neurogenesis, neuronal plasticity, and nerve remyelination [22,23]. Moreover, progesterone also participates in critical development events such as neuronal differentiation, neural circuit organization, brain sex differentiation, and oligodendrogenesis [51].…”

Section: Discussionmentioning

confidence: 99%

Progesterone through Progesterone Receptor B Isoform Promotes Rodent Embryonic Oligodendrogenesis

González-Orozco

Moral-Morales

2020

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Oligodendrocytes are the myelinating cells of the central nervous system (CNS). These cells arise during the embryonic development by the specification of the neural stem cells to oligodendroglial progenitor cells (OPC); newly formed OPC proliferate, migrate, differentiate, and mature to myelinating oligodendrocytes in the perinatal period. It is known that progesterone promotes the proliferation and differentiation of OPC in early postnatal life through the activation of the intracellular progesterone receptor (PR). Progesterone supports nerve myelination after spinal cord injury in adults. However, the role of progesterone in embryonic OPC differentiation as well as the specific PR isoform involved in progesterone actions in these cells is unknown. By using primary cultures obtained from the embryonic mouse spinal cord, we showed that embryonic OPC expresses both PR-A and PR-B isoforms. We found that progesterone increases the proliferation, differentiation, and myelination potential of embryonic OPC through its PR by upregulating the expression of oligodendroglial genes such as neuron/glia antigen 2 (NG2), sex determining region Y-box9 (SOX9), myelin basic protein (MBP), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP1), and NK6 homeobox 1 (NKX 6.1). These effects are likely mediated by PR-B, as they are blocked by the silencing of this isoform. The results suggest that progesterone contributes to the process of oligodendrogenesis during prenatal life through specific activation of PR-B.

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“…Progesterone promotes the proliferation of neural progenitor cells and dopaminergic neuronal differentiation in the developing CNS. Furthermore, it is involved in brain sexual differentiation and has been shown to stimulate myelination not only through increasing myelin synthesis in oligodendrocytes, but also by inducing the proliferation and promoting the differentiation of oligodendrocyte progenitor cells [36,37]. PPAR gamma activation increases proliferation and counteracts apoptosis in human and rodent neuronal stem cells, and is involved in neuronal differentiation, while PPAR alpha and beta are implicated in the maturation of astrocytes and oligodendrocytes, respectively [35].…”

Section: Pathways Linking Ed To Dntmentioning

confidence: 99%

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity

Lupu

Andersson

Bornehag

et al. 2020

IJMS

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Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.

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Progesterone Actions During Central Nervous System Development

Cited by 72 publications

References 140 publications

Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

Progesterone through Progesterone Receptor B Isoform Promotes Rodent Embryonic Oligodendrogenesis

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity

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