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Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
Oligodendrocyte mitochondria from 21-day-old Sprague-Dawley male rats were incubated with 100 nM (/sup 3/H)cholesterol. It yielded (/sup 3/H)pregnenolone at a rate of 2.5 +/- 0.7 and 5-(/sup 3/H)pregnene-3..beta..,20..cap alpha..-diol at a rate of 2.5 +/- 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19- to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with (/sup 3/H)mevalonolactone. (/sup 3/H)Cholesterol, (/sup 3/H)pregnenolone, and 5-(/sup 3/H)pregnene-3..beta..,20..cap alpha..-diol were characterized in cellular extracts. The formation of the /sup 3/H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of neurosteroids applied to ..delta../sup 5/-3..beta..-hydroxysteroids previously isolated from brain.
Research Organization:
Universite Paris-Sud, Bicetre (France)
OSTI ID:
6409041
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:23; ISSN PNASA
Country of Publication:
United States
Language:
English