Neurosteroids are steroids de novo synthesized in the brain or metabolized in situ by blood borne precursors. Neurosteroids influence brain function via both genomic and nongenomic mechanisms ; the first include the induction of progesterone receptors in cultured oligodendrocytes, the latter include the modulation of calcium channel and of chloride channel opening. Some neurosteroids act as GABA-A agonists, such as allopregnanolone and tetrahydrodesoxycorticosterone; others are GABA-A antagonists, such as DHEA and pregnanolone sulfate (Figure 1). Brain is the first known source of neurosteroids. Bixo et al. have evaluated women post-mortem concentrations of allopregnanolone in brain cortex, amygdala, hippocampus, caudate nucleus, putamen, thalamus, and the highest levels were observed in the substantia nigra and basal hypothalamus . The regional differences in brain steroid levels imply different local mechanisms for steroid uptake and binding. Brain concentrations of allopregnanolone were significantly higher in fertile women at luteal phase than in postmenopausal controls; this may depend on ovarian steroid production, indicating that the secretion pattern during the menstrual cycle is reflected in the brain . A5 androgens have also been measured in specific regions of cadaver brains and the central/plasmatic ratio of DHEA demonstrated a higher concentration of the steroid within the brain [1,3].
KeywordsDementia Cortisol Progesterone Androgen Fluoxetine
Unable to display preview. Download preview PDF.
- 18.Thijssen JHH, Nieuwenhuyse H. DHEA: A comprehensive review. New York: The Parthenon Publishing Group, 1999.Google Scholar
- 31.Monteleone P, Luisi M, Colurcio B, et al. Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa. Psycosomatic Medicine 2001; 63:62–68.Google Scholar
- 33.Luisi S, Petraglia F, Benedetto C, et al. Serum allopregnanolone levels in pregnant women: Changes during pregnancy, at delivery and in hypertensive patients. J Clin Endorinol Metab 2000; 83:2733–49.Google Scholar
- 42.Patchev VK, Shoaib M, Holsboer F, et al. The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience 1994; 62:265–71.PubMedCrossRefGoogle Scholar
- 43.Vallee M, Rivera JD, Koob GF, Purdy RH, Fitzgerald RL. Quantification of neurosteroids in rat plasma and brain following swim stress and allopregnanolone administration using negative chemical ionization gas chromatography/ mass spectrometry. Anal Biochem 2000 Dec l; 287(l):153–66.PubMedCrossRefGoogle Scholar
- 46.Berretini WH, Post RM. Gaba in affective illness. In: Post RM, Ballanger JC, editors. Ineurobilogy of mood disorders. Williams and Wilkins, Baltimore; 1984, 673–685.Google Scholar
- 48.van Goozen SHM, Matthys W, Cohen-Kettenis PT, Thijssen JHH, van Engeland II. Adrenal androgens and aggression in conduct disorder prepubertal boys and normal controls. Biol Psychiatry 1998; 43:145–53.Google Scholar
- 49.Roberts E. Dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) as neural facilitators: effects on brain tissue in culture and on memory in young and old mice: A cyclic GMP hypothesis of action of DHEA and DHEAS in nervous system and other tissues. In: Kalimi M, Regelson W, editors. The biologic role of dehydroepiandrosterone. Berlin, Walter de Gruyter; 1990, 13–42.Google Scholar
- 51.Wolkowitz OM, Reus VI, Manfredi F, Roberts E. Antiglucocorticoid effects in Alzheimer’s disease (reply). Am J Psychiatry 1992; 149:1126.Google Scholar