Cited by 201Neuroscience and Neuropharmacology ResearchEstrogen and related hormone effectsSexual Differentiation and Disorders

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Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system

Compagnone, N A, Bulfone, A, Rubenstein, J L, Mellon, S H·1995·Endocrinology

DOI 10.1210/endo.136.11.7588260

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Abstract

Neurosteroids are steroids that are synthesized de novo in the brain and include some classical (adrenal and gonadal steroids) and some unique brain-specific steroids. Neurosteroids are thought to mediate their action through ion gated channel receptors such as gamma-aminobutyric acid(A) and N-methyl-D-aspartate rather than through classical nuclear steroid hormone receptors. Some enzymes involved in neurosteroidogenesis have been identified as those found in steroidogenic tissues, and some may be unique to the brain. We previously demonstrated that the messenger RNAs (mRNA) for the cholesterol side-chain cleavage enzyme, cytochrome P450scc, and one form of 11 beta-hydroxylase, cytochrome P450c11 beta, are regionally expressed in the adult rat brain. However, cytochrome P450c17, which has 17-hydroxylase and 17,20-lyase activity and is thought to be required for the synthesis of dehydroepiandrosterone, was not detected in any region of the rat brain, even though dehydroepiandrosterone is one of the most abundant neuroactive steroids. We now demonstrate that P450c17 is expressed in the nervous system of the developing rodent embryo. By ribonuclease protection assays, P450c17 mRNA was found in the trunk but not in the head of rat embryos but reverse transcriptase-polymerase chain reaction analysis showed expression of P450c17 mRNA in the head of E15.5 to E19.5 rat embryos. Immunocytochemically detectable P450c17 protein was expressed in the nervous system as early as embryonic day E10.5 in the mouse, mainly in tissue derived from the neural crest. Neuronal cell bodies as well as fibers staining for P450c17 were observed in the central and peripheral nervous systems. The sites of P450c17 expression in the peripheral nervous system suggest it may be involved in a wide variety of sensory-motor functions. In the central nervous system, cell bodies expressing P450c17 are found in the hind brain, in mesencephalic nuclei, and in a region in the location of the locus coeruleus, but in cells distinct from those expressing the dopamine-beta-hydroxylase. Furthermore, its particular location and temporal expression in axons reaching the cortical areas suggest it is a marker for the axonal growth in this region, and that its neurosteroid product may be a signal for targeting cortical axons during embryogenesis.

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Authors: Compagnone, N. A., Bulfone, A., Rubenstein, J. L., & Mellon, S. H.
Affiliations: University of California, San Francisco (US)
ORCID: Rubenstein, J L
Mellon, S H
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1995-11
Volume: 136
Issue: 11
Pages: 5212-5223
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.136.11.7588260
OpenAlex: W2003054343
Semantic Scholar: 897468ac424340da27937ef47a2e152c1ebaad6c
Cited by: 201
References: 0
Citations by year: 2026: 2 · 2024: 1 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 8 · 2012: 6
FWCI: 2.13
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p30hd011979-20)
National Institute of Mental Health (R01 MH4942801, R01MH049428)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-11979, HD27970, R01HD027970)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Keywords: P450c17, steroidogenic enzymes, neurosteroidogenesis, neurosteroids, embryonic central nervous system, neural crest, axon growth, dehydroepiandrosterone, brain steroid metabolism, rat embryo, mouse embryo, hindbrain, locus coeruleus
MeSH terms: Animals, Base Sequence, Central Nervous System, Female, Humans, Immunohistochemistry, Male, Mice, Inbred BALB C, Molecular Sequence Data, RNA-Directed DNA Polymerase, RNA, Messenger, Steroid 17-alpha-Hydroxylase, DNA Probes, Gene Expression, Polymerase Chain Reaction, Rats, Sprague-Dawley, In Situ Hybridization, Fluorescent Antibody Technique, Indirect, Mice, Rats

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Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system

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