Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jan 1;90(1):85–88. doi: 10.1073/pnas.90.1.85

Steroids and their conjugates in the mammalian brain.

C Mathur 1, V V Prasad 1, V S Raju 1, M Welch 1, S Lieberman 1
PMCID: PMC45604  PMID: 8419947

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

PDF
85

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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. doi: 10.1016/0306-4530(90)90025-5. [DOI] [PubMed] [Google Scholar]
  2. Corpéchot C., Synguelakis M., Talha S., Axelson M., Sjövall J., Vihko R., Baulieu E. E., Robel P. Pregnenolone and its sulfate ester in the rat brain. Brain Res. 1983 Jun 27;270(1):119–125. doi: 10.1016/0006-8993(83)90797-7. [DOI] [PubMed] [Google Scholar]
  3. Flood J. F., Morley J. E., 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. doi: 10.1073/pnas.89.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Harrison N. L., Majewska M. D., Harrington J. W., Barker J. L. 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]
  5. Irwin R. P., Maragakis N. J., Rogawski M. A., Purdy R. H., Farb D. H., Paul S. M. Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons. Neurosci Lett. 1992 Jul 6;141(1):30–34. doi: 10.1016/0304-3940(92)90327-4. [DOI] [PubMed] [Google Scholar]
  6. Jo D. H., Abdallah M. A., Young J., Baulieu E. E., Robel P. Pregnenolone, dehydroepiandrosterone, and their sulfate and fatty acid esters in the rat brain. Steroids. 1989 Sep;54(3):287–297. doi: 10.1016/0039-128x(89)90003-2. [DOI] [PubMed] [Google Scholar]
  7. Jo D. H., Sánchez de la Peña S., Halberg F., Ungar F., Baulieu E. E., Robel P. Circadian-infradian rhythmic variation of brain neurosteroids in the female rat. Prog Clin Biol Res. 1990;341B:125–134. [PubMed] [Google Scholar]
  8. Knuppen R., Haupt O., Schramm W., Hoppen H. O. 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. doi: 10.1016/0022-4731(79)90291-7. [DOI] [PubMed] [Google Scholar]
  9. Lacroix C., Fiet J., Benais J. P., Gueux B., Bonete R., Villette J. M., 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. doi: 10.1016/0022-4731(87)91025-9. [DOI] [PubMed] [Google Scholar]
  10. Majewska M. D., Harrison N. L., Schwartz R. D., Barker J. L., Paul S. M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986 May 23;232(4753):1004–1007. doi: 10.1126/science.2422758. [DOI] [PubMed] [Google Scholar]
  11. Majewska M. D., Schwartz R. D. Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain? Brain Res. 1987 Feb 24;404(1-2):355–360. doi: 10.1016/0006-8993(87)91394-1. [DOI] [PubMed] [Google Scholar]
  12. McEwen B. S., De Kloet E. R., Rostene W. Adrenal steroid receptors and actions in the nervous system. Physiol Rev. 1986 Oct;66(4):1121–1188. doi: 10.1152/physrev.1986.66.4.1121. [DOI] [PubMed] [Google Scholar]
  13. Paul S. M., Purdy R. H. Neuroactive steroids. FASEB J. 1992 Mar;6(6):2311–2322. [PubMed] [Google Scholar]
  14. Prasad V. V., 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. doi: 10.1073/pnas.82.9.2657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Purdy R. H., Moore P. H., Jr, Rao P. N., Hagino N., Yamaguchi T., Schmidt P., Rubinow D. R., Morrow A. L., Paul S. M. Radioimmunoassay of 3 alpha-hydroxy-5 alpha-pregnan-20-one in rat and human plasma. Steroids. 1990 Jul;55(7):290–296. doi: 10.1016/0039-128x(90)90031-6. [DOI] [PubMed] [Google Scholar]
  16. Sjövall J., Axelson M. Newer approaches to the isolation, identification, and quantitation of steroids in biological materials. Vitam Horm. 1982;39:31–144. doi: 10.1016/s0083-6729(08)61135-8. [DOI] [PubMed] [Google Scholar]
  17. Turner D. M., Ransom R. W., Yang J. S., Olsen R. W. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES