Dr Jonathan Fry

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Personal Profile

Name: Jonathan Fry Email: j.fry@ucl.ac.uk
Title: Dr Tel: 020 7679 6214
Department: Neuro, Physiology & Pharmacology Fax:
Position: Senior Lecturer Address: Dept of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT
Research Domain: Basic Life Sciences, Experimental Medicine, Neuroscience, Personalised Medicine Web Page: Personal Web Page

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Research Description

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 γ-aminobutyric acid (GABA) and glutamate as well as σ-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, UCLH). Routine measurements employ radioimmunoassays. Radiolabelled steroids are also employed to investigate steroid metabolism both in vitro and in vivo.


Research Activities

Brain steroids

Brain steroids in steroid sulphatase deficient mice

GABA modulatory steroids in the brains of mutant mice insensitive to this action

Progesterone withdrawal in the rat as a model for understanding premenstrual dysphoria

Uptake and metabolism of steroid sulphates by adult male rat brain

Education Description

In addition to teaching Physiology to BSc and MBBS students I also took a lead in the development of and continue an active role in the delivery of the Natural Sciences BSc/MSci programme here at UCL. This programme enables students to follow courses to an advanced level in both the Faculty of Life Sciences and the Faculty of Mathematical and Physical Sciences.

I am Chair of the Board of Examiners in Physiology.   

UCL Collaborators

Prof Trevor Smart

External Collaborators

Dr Thelma Lovick; Dr William Davies; Dr Diana Dolman

Publications

    2014

    • Fry JP, Li KY, Devall AJ, Cockcroft S, Honour JW, Lovick TA (2014). Fluoxetine elevates allopregnanolone in female rat brain but inhibits a steroid microsomal dehydrogenase rather than activating an aldo-keto reductase.. Br J Pharmacol, , - . doi:10.1111/bph.12891
    • Trent S, Fry JP, Ojarikre OA, Davies W (2014). Altered brain gene expression but not steroid biochemistry in a genetic mouse model of neurodevelopmental disorder.. Mol Autism, 5(1), 21 - . doi:10.1186/2040-2392-5-21

    2011

    • Sujkovic E, Mileusnic R, Fry JP (2011). DHEA and Memory. In Watson RR (Ed.), DHEA in Human Health and Aging (pp. 399 - 413). : CRC Press.
    • Devall AJ, Fry JP, Honour JW, Lovick TA (2011). Short term, low dose fluoxetine treatment increases brain allopregnanolone concentrations in female rats and abolishes estrous cycle-related stress-induced hyperalgesia.
    • Devall AJ, Fry JP, Honour JW, Lovick TA (2011). Brain progesterone metabolism in rats following acute fluoxetine treatment: Sex differences and anxiolytic effects in females.

    2009

    • Sujkovic E, Mileusnic R, Fry JP (2009). Metabolism of neuroactive steroids in day-old chick brain. Journal of Neurochemistry, 109, 348 - 359. doi:10.1111/j.1471-4159.2009.05965.x

    2008

    • Sotiropoulos I, Catania C, Riedemann T, Fry JP, Breen KC, Michaelidis TM, Almeida OF (2008). Glucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tau. Journal of Neurochemistry, 107(2), 385 - 397. doi:10.1111/j.1471-4159.2008.05613.x

    2007

    • Nicolas LB, Fry JP (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. doi:10.1016/j.brainres.2007.07.078
    • Sujkovic E, Mileusnic R, Fry JP, Rose SPR (2007). Temporal effects of dehydroepiandrosterone sulfate on memory formation in day-old chicks. Neuroscience, 148, 375 - 384. doi:10.1016/j.neuroscience.2007.06.006

    2006

    • Ebner MJ, Corol DI, Havlikova H, Honour JW, Fry JP (2006). Identification of neuroactive steroids and their precursors and metabolites in adult male rat brain. Endocrinology, 147(1), 179 - 190. doi:10.1210/en.2005-1065

    2001

    • Ebner MJ, Honour JW, Fry JP (2001). Free steroids and their sulphate esters in male rat brain.

    1999

    • Fry JP (1999). Steroids,brains and behaviour. Wellcome News, (19), 36 - 36.
    • Ebner MJ, Honour JW, Fry JP (1999). Extraction, fractionation and mass-spectroscopic identification of steroids from brain tissue.

    1998

    1997

    • Corpechot C, Collins BE, Carey MP, Tsouros A, Robel P, Fry JP (1997). Brain neurosteroids during the mouse oestrous cycle. Brain Research, 766, 276 - 280. doi:10.1016/S0006-8993(97)00749-X

    1996

    • O'Connor V, Phelan PP, Fry JP (1996). Interactions of glycine and strychnine with their receptor recognition sites in mouse spinal cord.. Neurochem Int, 29(4), 423 - 434. doi:10.1016/0197-0186(95)00160-3

    1995

    • Carey MP, Fry JP (1995). Evaluation of animal welfare by the self-expression of an anxiety state.. Lab Anim, 29(4), 370 - 379. doi:10.1258/002367795780739999
    • Collins BE, Corpéchot C, Carey MP, Tsouros A, Robel P, Fry JP (1995). Brain progesterone metabolism during the mouse estrus cycle.

    1994

    • Carey MP, Aniszewski CA, Fry JP (1994). Metabolism of progesterone in mouse brain.. J Steroid Biochem Mol Biol, 50(3-4), 213 - 217. doi:10.1016/0960-0760(94)90031-0

    1993

    • Carey MP, Fry JP (1993). A behavioural and pharmacological evaluation of the discriminative stimulus induced by pentylenetetrazole in the pig.. Psychopharmacology (Berl), 111(2), 244 - 250. doi:10.1007/BF02245531
    • Carey MP, Aniszewski CA, Fry JP (1993). Progesterone metabolism in mouse brain homogenates.

    1992

    • Carey MP, Fry JP, White DG (1992). The detection of changes in psychological state using a novel pharmacological conditioning procedure.. J Neurosci Methods, 43(1), 69 - 76. doi:10.1016/0165-0270(92)90068-O
    • Carey MP, Billing AE, Fry JP (1992). Fluctuations in responses to diazepam during the oestrous cycle in the mouse.. Pharmacol Biochem Behav, 41(4), 719 - 725. doi:10.1016/0091-3057(92)90218-5
    • Carey MP, Rickets C, Fry JP (1992). An additional pathway for progesterone metabolism in mouse brain.

    1991

    • O'Connor VM, Fry JP (1991). Modification of arginine residues reveals [3H]-strychnine binding sites sensitive to use dependent cation channel blockers in mouse spinal cord membranes.

    1990

    • O'Connor VM, de Alwis MA, Khan JA, Fry JP (1990). Chemical modification of spinal cord membranes reveals [3H]strychnine binding sites that are not located on the 48 kDa subunit of the synaptic glycine receptor..
    • Carey MP, Fry JP (1990). Altered responses to diazepam during the mouse oestrous cycle.
    • Carey MP, Fry JP, White DG (1990). Anxiety and the discriminative stimulus induced by pentylenetetrazol in the pig.

    1989

    • Phelan PP, Fry JP, Martin IL, Johnston GA (1989). Polyclonal antibodies to the glycine receptor antagonist strychnine.. J Neurochem, 52(5), 1481 - 1486. doi:10.1111/j.1471-4159.1989.tb09197.x
    • Biscoe TJ, Duchen MR, Fry JP, Rickets C (1989). Purification and actions of endogenous benzodiazepine like immunoreactivity isolated from the brain of the mouse.
    • Carey MP, Fry JP (1989). An evaluation of light aversion as a measure of anxiety in the mouse.
    • Carey MP, Fry JP, Jones AT, Stephens DB, West DC, White DG (1989). Pharmacological conditioning with anxiogenic agents in the pig.

    1988

    • O'Connor VM, Phelan PP, Fry JP (1988). Modification of arginine residues reveals additional specific strychnine binding sites in mouse spinal cord membranes.
    • Martin IL, Fry JP (1988). Endogenous ligands for the benzodiazepine receptor.. Neurochem Int, 13(1), 17 - 19. doi:10.1016/0197-0186(88)90097-6

    1987

    • FRY J, JOHNSTON G, MARTIN I, PHELAN P, RICKETS C (1987). STRYCHNINE-LIKE IMMUNOREACTIVITY IN GLUTARALDEHYDE-FIXED SECTIONS OF MOUSE CENTRAL-NERVOUS-SYSTEM.
    • FRY J, RICKETS C, MARTIN I (1987). POLYCLONAL ANTIBODIES TO AGONIST BENZODIAZEPINES. BIOCHEM PHARMACOL, 36(21), 3763 - 3770. doi:10.1016/0006-2952(87)90032-3

    1986

    • AYAD V, FRY J, MARTIN I, RICKETS C (1986). IMMUNOCHEMICAL EVIDENCE FOR AN ENDOGENOUS BENZODIAZEPINE RECEPTOR LIGAND IN THE BRAIN OF THE MOUSE.
    • Fry JP, Phelan PP (1986). Interactions of glycine receptor ligands in the normal mouse spinal cord.
    • Billing AE, Fry JP, Read GL (1986). Changes in sensitivity to diazepam during the oestrous cycle in the mouse.
    • Biscoe TJ, Fry JP, Duchen MR (1986). Inhibitory amino acid receptors in the nervous system of normal and mutant mice.

    1985

    • FRY J, Rickets C, Biscoe TJ (1985). On the location of γ-aminobutyrate and benzodiazepine receptors in the cerebellum of the normal C3H and Lurcher mutant mouse. Neuroscience, 14, 1091 - 1101. doi:10.1016/0306-4522(85)90279-9

    1984

    • Biscoe TJ, Fry JP, Rickets C (1984). Changes in benzodiazepine receptor binding as seen autoradiographically in the central nervous system of the spastic mouse. J. Physiol., 352, 509 - 516.
    • Biscoe TJ, Fry JP (1984). GABA and benzodiazepine receptors in neurologically mutant mice. In Bowery NG (Ed.), Actions and Interactions of GABA and Benzodiazepines (pp. 217 - 237). : Raven Press.
    • Biscoe TJ, Fry JP, Rickets C, Wu J-Y (1984). Immunocytochemical visualisation of L glutamate decarboxylase in the cerebellum of the normal and the mutant mouse Lurcher.
    • Biscoe TJ, Fry JP, Rickets C (1984). Autoradiography of benzodiazepine receptor binding in the central nervous system of the normal C57BL6J mouse. J. Physiol., 352, 495 - 508.

    1983

    • Fry JP, Magee RS (1983). Fluctuations in the binding of a benzodiazepine receptor ligand during the oestrous cycle in the brain of the mouse.

    1982

    • Fry JP, McHanwell S (1982). Elevated binding of GABA and benzodiazepine receptor ligands in the forebrain of the mutant mouse jimpy.
    • Biscoe TJ, Fry JP (1982). Some pharmacological studies on the spastic mouse. Brit. J. Pharmac., 75, 23 - 35.
    • SHARMAN D, MANN S, FRY J, BANNS H, STEPHENS D (1982). CEREBRAL DOPAMINE METABOLISM AND STEREOTYPED BEHAVIOR IN EARLY-WEANED PIGLETS. NEUROSCIENCE, 7(8), 1937 - 1944. doi:10.1016/0306-4522(82)90008-2
    • Fry JP, Magee RS (1982). Binding of GABA and benzodiazepine receptor ligands in the spinal cord of the mutant mouse Sprawling.
    • Biscoe TJ, Fry JP, Rickets C (1982). GABA and benzodiazepine receptors in the cerebellum of the mutant mouse Lurcher.

    1981

    • BISCOE TJ, FRY JP, MARTIN IL, RICKETS C (1981). BINDING OF GABA AND BENZODIAZEPINE RECEPTOR LIGANDS IN THE SPINAL-CORD OF THE SPASTIC MOUSE.
    • Fry JP, Sharman DF, Stephens DB (1981). Cerebral dopamine, apomorphine and oral activity in the neonatal pig. Journal of Veterinary Pharmacology and Therapeutics, 4, 193 - 207. doi:10.1111/j.1365-2885.1981.tb00730.x

    1980

    • FRY J, ZIEGLGANSBERGER W, HERZ A (1980). DEVELOPMENT OF ACUTE OPIOID TOLERANCE AND DEPENDENCE IN RAT STRIATAL NEURONS. N-S ARCH PHARMACOL, 313(2), 145 - 149. doi:10.1007/BF00498571
    • FRY J, HERZ A, ZIEGLGANSBERGER W (1980). DEMONSTRATION OF NALOXONE-PRECIPITATED OPIATE WITHDRAWAL ON SINGLE NEURONS IN THE MORPHINE-TOLERANT-DEPENDENT RAT-BRAIN. BRIT J PHARMACOL, 68(3), 585 - 592.
    • Zieglgänsberger W, Lambert LA, Fry JP (1980). Iontophoretically applied morphine and met enkephalin may interact with different receptors in the brain. In Way EL (Ed.), Endogenous and Exogenous Opiate Agonists and Antagonists (pp. 139 - 142). : Pergamon Press.
    • Biscoe TJ, Fry JP (1980). Pharmacological studies of the spastic mouse.

    1979

    • Herz A, Bläsig J, Fry JP, Höllt V, Meyer G, Przewlocki R (1979). Opiate receptors, their endogenous ligands and the development of tolerance/dependence.
    • FRY JP, HERZ A, ZIEGLGANSBERGER W (1979). LACK OF BARIUM-INDUCED EXCITATION IN THE CEREBRAL-CORTEX AND HIPPOCAMPUS OF MORPHINE TOLERANT-DEPENDENT RATS.
    • FRY J, ZIEGLGANSBERGER W (1979). COMPARISON OF THE EFFECTS OF GABA AND ENKEPHALIN ON SYNAPTICALLY EVOKED ACTIVITY IN THE RAT STRIATUM. APPL NEUROPHYSIOL, 42(1-2), 54 - 56. doi:10.1159/000102337
    • FRY J, ZIEGLGANSBERGER W, HERZ A (1979). SPECIFIC VERSUS NONSPECIFIC ACTIONS OF OPIOIDS ON HIPPOCAMPAL NEURONS IN THE RAT-BRAIN. BRAIN RES, 163(2), 295 - 305. doi:10.1016/0006-8993(79)90357-3

    1978

    • FRY J, Zieglgänsberger W, Herz A (1978). Tachyphylaxis to enkephalin - tolerance and dependence at the single neurone level?. In Ryall RW, Kelly JS (Ed.), Iontophoresis and Transmitter Mechanisms in the Mammalian Central Nervous System (pp. 323 - 325). : Elsevier/North-Holland Biomedical Press.
    • FRY J, Zieglgänsberger W, Herz A (1978). Single neurone studies of opioid tolerance and dependence. In van Ree JM, Terenius L (Ed.), Characteristics and Function of Opioids (pp. 99 - 100). : Elsevier/North-Holland Biomedical Press.
    • Zieglgänsberger W, Fry JP (1978). Actions of opioids on single neurones. In Herz A (Ed.), Developments in Opiate Research (pp. 193 - 239). : Marcel Dekker.
    • FRY J, HERZ A, ZIEGLGANSBERGER W (1978). NONSPECIFIC ACTIONS OF OPIOIDS IN RAT HIPPOCAMPUS.

    1977

    • Herz A, Zieglgänsberger W, Schulz R, Satoh M, Fry JP (1977). Neuronal aspects of opiate dependence and tolerance in comparison to central depressants. In Gross MM (Ed.), Alcohol Intoxication and Withdrawal (pp. 117 - 139). : Plenum Press.

    1976

    • ZIEGLGANSBERGER W, FRY J, HERZ A, MORODER L, WUNSCH E (1976). ENKEPHALIN-INDUCED INHIBITION OF CORTICAL-NEURONS AND LACK OF THIS EFFECT IN MORPHINE TOLERANT-DEPENDENT RATS. BRAIN RES, 115(1), 160 - 164. doi:10.1016/0006-8993(76)90832-5
    • FRY J, SHARMAN D, STEPHENS D (1976). ONTOGENESIS OF CEREBRAL DOPAMINE METABOLISM IN PIG.
    • FRY J, SHARMAN D, STEPHENS D (1976). EFFECT OF APOMORPHINE ON ORAL BEHAVIOR IN PIGLETS.
    • FRY J, Sharman DF (1976). The effects of tranquillizing drugs on the metabolism of transmitter substances in the central nervous system. In Bradford HF, Marsden CD (Ed.), Biochemistry and Neurology (pp. 57 - 71). : Academic Press.
    • Zieglgänsberger W, Fry JP (1976). Actions of enkephalin on cortical and striatal neurones of naive and morphine tolerant/dependent rats. In Kosterlitz HW (Ed.), Opiates and Endogenous Opioid Peptides (pp. 231 - 238). : Elsevier/North-Holland Biomedical Press.
    • FRY J, Sharman DF, Stephens DB (1976). A possible neurochemical basis for abnormal behaviour in farm animals. In Usdin E, Kvetnansky R, Kopin I (Ed.), Catecholamines and Stress (pp. 603 - 614). : Pergamon Press.

    1975

    • BARRAND M, CALLINGHAM B, FRY J, MITCHINSON M, SHARMAN D (1975). RADIOCHEMICAL ASSAY OF CATECHOLAMINES IN BLOOD-PLASMA.
    • STEPHENS DB, SHARMAN DF, FRY JP (1975). MEASUREMENT OF STRESS IN FARM ANIMALS - REVIEW OF EXPERIMENTAL METHODS USED IN LABORATORY TO STUDY EMOTIONAL BEHAVIOR. In (Ed.), (pp. 109 - 109). : BRITISH VETERINARY ASSOC.

    1974

    • FRY JP, HOUSE CR, SHARMAN DF (1974). ANALYSIS OF CATECHOLAMINE CONTENT OF SALIVARY-GLAND OF COCKROACH.