Proc Natl Acad Sci U S A 90(1): 85-88
Steroids and their conjugates in the mammalian brain.
Abstract
Five steroids--3 beta-hydroxypregn-5-en-20-one (pregnenolone; P), 3 beta-hydroxy-5 alpha-pregnan-20-one (3 beta-AP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-AP), 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone; D), and 3 beta-hydroxy-5 alpha-androstan-17-one (EpiA)--were extracted from the brains of adult male rats, rabbits, and dogs. The steroids exist in this organ as unconjugated compounds and as sulfates, lipoidal esters, and sulfolipids. The techniques for separating these four classes of steroids from each other and for separating the five steroids from each other are described. In all cases, the steroids were identified by their retention time (Rt) on HPLC, their Rt by gas chromatography, and by selected ion monitoring of their mass spectra. The latter were also used for quantification. In their reaction toward organic bases, the sulfolipid conjugates resemble previously described sulfolipids of cholesterol and sitosterol. These conjugates are relatively abundant in brain, particularly those of P and D, and this suggests that, in the search for the physiological significance of these brain constituents, these conjugates warrant attention.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (755K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Corpéchot C, Synguelakis M, Talha S, Axelson M, Sjövall J, Vihko R, Baulieu EE, Robel P. Pregnenolone and its sulfate ester in the rat brain. Brain Res. 1983 Jun 27;270(1):119–125. [PubMed] [Google Scholar]
- Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986 May 23;232(4753):1004–1007. [PubMed] [Google Scholar]
- Irwin RP, Maragakis NJ, Rogawski MA, Purdy RH, Farb DH, Paul SM. Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons. Neurosci Lett. 1992 Jul 6;141(1):30–34. [PubMed] [Google Scholar]
- Jo DH, Abdallah MA, Young J, Baulieu EE, Robel P. Pregnenolone, dehydroepiandrosterone, and their sulfate and fatty acid esters in the rat brain. Steroids. 1989 Sep;54(3):287–297. [PubMed] [Google Scholar]
- Paul SM, Purdy RH. Neuroactive steroids. FASEB J. 1992 Mar;6(6):2311–2322. [PubMed] [Google Scholar]
- Lacroix C, Fiet J, Benais JP, Gueux B, Bonete R, Villette JM, Gourmel B, Dreux C. Simultaneous radioimmunoassay of progesterone, androst-4-enedione, pregnenolone, dehydroepiandrosterone and 17-hydroxyprogesterone in specific regions of human brain. J Steroid Biochem. 1987 Sep;28(3):317–325. [PubMed] [Google Scholar]
- Bixo M, Bäckström T. Regional distribution of progesterone and 5 alpha-pregnane-3,20-dione in rat brain during progesterone-induced "anesthesia". Psychoneuroendocrinology. 1990;15(2):159–162. [PubMed] [Google Scholar]
- Purdy RH, Moore PH, Jr, Rao PN, Hagino N, Yamaguchi T, Schmidt P, Rubinow DR, Morrow AL, Paul SM. Radioimmunoassay of 3 alpha-hydroxy-5 alpha-pregnan-20-one in rat and human plasma. Steroids. 1990 Jul;55(7):290–296. [PubMed] [Google Scholar]
- Jo DH, Sánchez de la Peña S, Halberg F, Ungar F, Baulieu EE, Robel P. Circadian-infradian rhythmic variation of brain neurosteroids in the female rat. Prog Clin Biol Res. 1990;341B:125–134. [PubMed] [Google Scholar]
- Prasad VV, el-Maraghy E, Ponticorvo L, Lieberman S. Detection in extracts of bovine brain of lipophilic complexes of sulfate esters of cholesterol and beta-sitosterol. Proc Natl Acad Sci U S A. 1985 May;82(9):2657–2659.[PMC free article] [PubMed] [Google Scholar]
- Sjövall J, Axelson M. Newer approaches to the isolation, identification, and quantitation of steroids in biological materials. Vitam Horm. 1982;39:31–144. [PubMed] [Google Scholar]
- Knuppen R, Haupt O, Schramm W, Hoppen HO. Selected ion monitoring: a new approach for the specific determination of steroids in the lower picogram range. J Steroid Biochem. 1979 Jul;11(1A):153–160. [PubMed] [Google Scholar]
- McEwen BS, De Kloet ER, Rostene W. Adrenal steroid receptors and actions in the nervous system. Physiol Rev. 1986 Oct;66(4):1121–1188. [PubMed] [Google Scholar]
- Majewska MD, Schwartz RD. Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain? Brain Res. 1987 Feb 24;404(1-2):355–360. [PubMed] [Google Scholar]
- Harrison NL, Majewska MD, Harrington JW, Barker JL. Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex. J Pharmacol Exp Ther. 1987 Apr;241(1):346–353. [PubMed] [Google Scholar]
- Turner DM, Ransom RW, Yang JS, Olsen RW. Steroid anesthetics and naturally occurring analogs modulate the gamma-aminobutyric acid receptor complex at a site distinct from barbiturates. J Pharmacol Exp Ther. 1989 Mar;248(3):960–966. [PubMed] [Google Scholar]
- Flood JF, Morley JE, Roberts E. Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1567–1571.[PMC free article] [PubMed] [Google Scholar]