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; 17β-hydroxy-11β-(4-methylaminophenyl)-17α-(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 3α,5α-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.
| Original language | English |
|---|---|
| Pages (from-to) | 6221-6232 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience |
| Volume | 21 |
| Issue number | 16 |
| Publication status | Published - Aug 15 2001 |
| Externally published | Yes |
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Keywords
- 3α,5α -tetrahydroprogesterone
- Cerebellar cortical formation
- Dendritic outgrowth
- Development
- Genomic action
- Neurosteroids
- Progesterone
- Progesterone receptor
- Purkinje cell
- Synaptogenesis
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Effects of progesterone synthesized de novo in the developing purkinje cell on its dendritic growth and synaptogenesis. / Sakamoto, Hirotaka; Ukena, Kazuyoshi; Tsutsui, Kazuyoshi.
In: Journal of Neuroscience, Vol. 21, No. 16, 15.08.2001, p. 6221-6232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of progesterone synthesized de novo in the developing purkinje cell on its dendritic growth and synaptogenesis
AU - Sakamoto, Hirotaka
AU - Ukena, Kazuyoshi
AU - Tsutsui, Kazuyoshi
PY - 2001/8/15
Y1 - 2001/8/15
N2 - 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; 17β-hydroxy-11β-(4-methylaminophenyl)-17α-(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 3α,5α-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.
AB - 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; 17β-hydroxy-11β-(4-methylaminophenyl)-17α-(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 3α,5α-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.
KW - 3α,5α -tetrahydroprogesterone
KW - Cerebellar cortical formation
KW - Dendritic outgrowth
KW - Development
KW - Genomic action
KW - Neurosteroids
KW - Progesterone
KW - Progesterone receptor
KW - Purkinje cell
KW - Synaptogenesis
UR - http://www.scopus.com/inward/record.url?scp=0035882468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035882468&partnerID=8YFLogxK
M3 - Article
C2 - 11487645
AN - SCOPUS:0035882468
VL - 21
SP - 6221
EP - 6232
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 16
ER -