title: Expression of P450c17 in the human fetal nervous system.
abstract: P450c17 catalyzes steroid 17α-hydroxylase and 17,20 lyase activities. P450c17 is expressed in human fetal and postnatal adrenals and gonads and in the developing mouse nervous system, but little is known about its expression in the human nervous system. We obtained portions of 9-, 10-, and 11-wk gestation human fetuses and delineated the pattern of expression of P450c17 in their peripheral nervous systems by immunocytochemistry using the P450c17 antiserum previously used to characterize P450c17 in the mouse brain. P450c17 was readily detected in the dorsal root ganglia (DRG) and spinal cord. Neural structures were identified with antisera to the cytoskeletal protein neural cell adhesion molecule; DRG were identified with antisera to the neuronal transcription factor BRN3A and neurotrophin receptor tropomyosin-receptor-kinase B. The identification of P450c17 was confirmed using commercial antisera directed against different domains of P450c17 and by using antisera immunodepleted with authentic human P450c17. We also found expression of the P450 cholesterol side-chain cleavage enzyme (P450scc) in the spinal cord and DRG. Expression of P450scc is limited to cell bodies; unlike P450c17, we never detected P450scc in fiber tracts. Catalysis by P450c17 requires electron donation from P450 oxidoreductase (POR). Dual-label immunohistochemistry detected P450c17 and POR colocalized in DRG bundles, but some fibers containing P450c17 lacked POR. These data suggest that neurosteroids synthesized via these two enzymes may act in the developing human nervous system. The expression of P450c17 in structures lacking POR means that P450c17 may not be steroidogenic in those locations, suggesting that P450c17 may have additional functions that do not require POR.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Science, University of California, San Francisco, 513 Parnassus Avenue, Box 0556, San Francisco, California 94143-0556, USA.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Schonemann
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: Meng Kian
authors.initials: MK
authors.lastname: Tee
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Mellon
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000201:enzymology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005333:Fetus / Q000201:enzymology*; D005727:Ganglia, Spinal / Q000196:embryology / Q000201:enzymology*; D006801:Humans; D013116:Spinal Cord / Q000196:embryology / Q000201:enzymology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D015096:3-Hydroxysteroid Dehydrogenases; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme