Steroids in the nervous system

Jonathan Fry
Senior Lecturer Tel: +44 (0)20 7679 6214
Email: j.fry@ucl.ac.uk

Research

Steroid hormones have long been known to enter the mammalian nervous system to influence its development and function. More recently, some steroids have also been shown to be present in brain tissue independently of peripheral endocrine sources, the so-called neurosteroids. Altogether, these brain steroids are of profound physiological significance and apart from well-established sites of action through transcription factors are also known to have more rapid non-genomic effects at neurotransmitter receptors, such as those for gamma-aminobutyric acid (GABA) and glutamate as well as sigma-receptors and voltage-gated ion channels. Despite the above background, little is known of the actual steroid content of the brain, of the relative contributions from peripheral versus central sources or of the metabolic pathways for steroid activation and inactivation in this tissue. Our research is focused on these issues. We have developed procedures for the extraction and fractionation of free steroids and their sulphate esters from brain tissue. For unequivocal identification, these steroids are then derivatised and analysed by gas capillary chromatography-electron impact mass spectrometry (in collaboration with Dr John W. Honour, Dept. of Chemical Pathology). Routine measurements employ radioimmunoassays. Radiolabelled steroids are also employed to investigate steroid metabolism both in vitro and in vivo. Current projects are as follows: 1. A collaboration with Dr D Dolman and others at Kings College London to study the uptake and metabolism of steroid sulphates by the rat brain. 2. A collaboration with the group of Dr T Lovick at the University of Birmingham to assay progesterone and its metabolites in rat brain during the ovarian cycle and during progesterone withdrawal. These measurements are made in relation to anxiety and pain thresholds and with implications for the mechanisms of premenstrual dysphoric disorder (PMDD.)

Selected publications:

  • Sujkovic,E., Mileusnic,R., Fry,J.P. (2009). Metabolism of neuroactive steroids in day-old chick brain. Journal of Neurochemistry 109, 348-359. ISSN: 0022-3042
  • Sotiropoulos,I., Catania,C., Riedemann,T., Fry,J.P., Breen,K.C., Michaelidis,T.M., Almeida,O.F. (2008). Glucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tau. Journal of Neurochemistry 107(2), 385-397.
  • Nicolas L.B., Fry J.P. (2007). The steroid sulfatase inhibitor COUMATE attenuates rather than enhances access of dehydroepiandrosterone sulfate to the brain in the mouse. Brain Research 1174, 92-96.
  • Sujkovic,E., Mileusnic,R., Fry,J.P., Rose,S.P.R. (2007). Temporal effects of dehydroepiandrosterone sulfate on memory formation in day-old chicks. Neuroscience 148, 375-384.
  • Ebner,M.J., Corol,D.I., Havlikova,H., Honour,J.W., Fry,J.P. (2006). Identification of neuroactive steroids and their precursors and metabolites in adult male rat brain. Endocrinology 147(1), 179-190.
  • Fry,J.P., Honour,J.W. (1998). Understanding premenstrual syndrome. The Lancet 351, 1511-1511.
  • Corpechot,C., Collins,B.E., Carey,M.P., Tsouros,A., Robel,P., Fry,J.P. (1997). Brain neurosteroids during the mouse oestrous cycle. Brain Research 766, 276-280.