The central nervous system (CNS) is considered a target structure for the action of all the classes of hormonal steroids produced by the organism. Well-characterized genomic and less well-understood membrane mechanisms of action are probably involved in the steroid modulation of brain activities. Moreover, some classes of steroids need to be converted into "active" metabolites before interacting with their effector systems. In particular, testosterone (T) exerts many of its effects after conversion to 5 alpha-dihydrotestosterone (DHT) and estrogens. The CNS possesses both the 5 alpha-reductase, the enzyme which produces DHT and the aromatase which transforms T into estrogens; however, the relative role and distribution of these enzymes in the various structural components of the CNS has not been clarified so far. The 5 alpha-reductase has been found to be present in high concentrations in brain white matter structures because these are particularly rich in myelin membranes, to which the enzymatic activity appears to be associated. This membrane localization might suggest a possible involvement of steroidal 5 alpha-reduced metabolites in membrane-mediated events in the CNS. Moreover, the distribution of 5 alpha-reductase was studied in neurons, astrocytes and oligodendrocytes isolated from the brain of male rats by density gradient ultracentrifugation, as well as in neurons and glial cells grown in culture. The aromatase activity was also evaluated in neurons and glial cells grown in culture and in isolated oligodendrocytes. Among the three cell types isolated, neurons appear to be more active than oligodendrocytes and astrocytes, respectively, in converting T into DHT. Also, in cell culture experiments, neurons are more active in forming DHT than glial cells. Only neurons possess aromatase activity, while glial cells are apparently unable to aromatize T.

Testosterone metabolism in brain cells and membranes / F. Celotti, R. C. Melcangi, P. Negri-Cesi, A. Poletti. - In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY. - ISSN 0960-0760. - 40:4-6(1991), pp. 673-678. ((Intervento presentato al 8. convegno 8th International Congress on Hormonal Steroids tenutosi a The Hague, The Netherland nel 1990.

Testosterone metabolism in brain cells and membranes

F. Celotti
Primo
;
R. C. Melcangi
Secondo
;
P. Negri-Cesi
Penultimo
;
A. Poletti
Ultimo
1991

Abstract

The central nervous system (CNS) is considered a target structure for the action of all the classes of hormonal steroids produced by the organism. Well-characterized genomic and less well-understood membrane mechanisms of action are probably involved in the steroid modulation of brain activities. Moreover, some classes of steroids need to be converted into "active" metabolites before interacting with their effector systems. In particular, testosterone (T) exerts many of its effects after conversion to 5 alpha-dihydrotestosterone (DHT) and estrogens. The CNS possesses both the 5 alpha-reductase, the enzyme which produces DHT and the aromatase which transforms T into estrogens; however, the relative role and distribution of these enzymes in the various structural components of the CNS has not been clarified so far. The 5 alpha-reductase has been found to be present in high concentrations in brain white matter structures because these are particularly rich in myelin membranes, to which the enzymatic activity appears to be associated. This membrane localization might suggest a possible involvement of steroidal 5 alpha-reduced metabolites in membrane-mediated events in the CNS. Moreover, the distribution of 5 alpha-reductase was studied in neurons, astrocytes and oligodendrocytes isolated from the brain of male rats by density gradient ultracentrifugation, as well as in neurons and glial cells grown in culture. The aromatase activity was also evaluated in neurons and glial cells grown in culture and in isolated oligodendrocytes. Among the three cell types isolated, neurons appear to be more active than oligodendrocytes and astrocytes, respectively, in converting T into DHT. Also, in cell culture experiments, neurons are more active in forming DHT than glial cells. Only neurons possess aromatase activity, while glial cells are apparently unable to aromatize T.
Animals; Cholestenone 5 alpha-Reductase; Brain; Myelin Sheath; Rats; Testosterone; Aromatase; Cells, Cultured; Neuroglia; Neurons; Cell Membrane; Dihydrotestosterone; Oxidoreductases
Settore BIO/09 - Fisiologia
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore MED/13 - Endocrinologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/182314
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