Cited by 193Neuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanismsSteroid Chemistry and Biochemistry

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Effects of Progesterone Synthesized De Novo in the Developing Purkinje Cell on Its Dendritic Growth and Synaptogenesis

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Sakamoto, Hirotaka, Ukena, Kazuyoshi, Tsutsui, Kazuyoshi·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-16-06221.2001PMC PMC6763166

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Abstract

De novo steroidogenesis from cholesterol is a conserved property of vertebrate brains, and such steroids synthesized de novo in the brain are called neurosteroids. The identification of neurosteroidogenic cells is essential to the understanding of the physiological role of neurosteroids in the brain. We have demonstrated recently that neuronal neurosteroidogenesis occurs in the brain and indicated that the Purkinje cell actively synthesizes several neurosteroids de novo from cholesterol in vertebrates. Interestingly, in the rat, this neuron actively synthesizes progesterone de novo from cholesterol only during neonatal life, when cerebellar cortical formation occurs most markedly. Therefore, in this study, the possible organizing actions of progesterone during cerebellar development have been examined. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone promotes dose-dependent dendritic outgrowth of Purkinje cells but dose not affect their somata. This effect was blocked by the anti-progestin RU 486 [mifepristone; 17beta-hydroxy-11beta-(4-methylaminophenyl)-17alpha-(1-propynyl) estra-4,9-dien-3 one-6-7]. In vivo administration of progesterone to pups further revealed an increase in the density of Purkinje spine synapses electron microscopically. In contrast to progesterone, there was no significant effect of 3alpha,5alpha-tetrahydroprogesterone, a progesterone metabolite, on Purkinje cell development. Reverse transcription-PCR-Southern and immunocytochemical analyses showed that intranuclear progesterone receptors were expressed in Purkinje cells. These results suggest that progesterone promotes both dendritic outgrowth and synaptogenesis in Purkinje cells through intranuclear receptor-mediated mechanisms during cerebellar development. Such organizing actions may contribute to the formation of the cerebellar neuronal circuit.

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Authors: Sakamoto, H., Ukena, K., & Tsutsui, K.
Affiliations: Hiroshima University (JP)
ORCID: Sakamoto, Hirotaka
Ukena, Kazuyoshi
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-08-15
Volume: 21
Issue: 16
Pages: 6221-6232
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-16-06221.2001
PMC: PMC6763166
OpenAlex: W1783731643
Semantic Scholar: 2b9eec77bf495ccf9efdb769ce7bc68a15546ed9
Cited by: 193
References: 64
Citations by year: 2026: 1 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 9 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 16
FWCI: 4.05
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: University of Central Lancashire
Japan Society for the Promotion of Science (11354010, 12440233)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
Keywords: progesterone, neurosteroidogenesis, Purkinje cells, dendritic outgrowth, synaptogenesis, cerebellar development, RU486, cerebellar slice cultures, neural circuit formation
MeSH terms: Animals, Animals, Newborn, Cerebellum, Dendrites, Dose-Response Relationship, Drug, Female, Hormone Antagonists, Male, Pregnanolone, Progesterone, Purkinje Cells, Rats, Inbred F344, Receptors, Progesterone, RNA, Messenger, Synapses, Mifepristone, Receptors, Cytoplasmic and Nuclear, Rats, Calbindins, S100 Calcium Binding Protein G, In Vitro Techniques

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Effects of Progesterone Synthesized De Novo in the Developing Purkinje Cell on Its Dendritic Growth and Synaptogenesis

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