7alpha-HYDROXYPREGNENOLONE ACTS AS A SEROTONIN-INDUCING FACTOR TO INCREASE LOCOMOTOR ACTIVITY VIA CORTICOSTERONE ACTION UNDER STRESS
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1
Waseda University, Department of Biology, Japan
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2
Tokyo Gakugei University, Department of Biology, Faculty of Education, Japan
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3
University of Rouen, INSERM U982, European Institute for Peptide Research, France
It is now established that steroids can be synthesized de novo in the central and peripheral nervous systems. Such steroids are called “neurosteroids”, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our previous studies have demonstrated that the brain of amphibians possesses the key steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones, and other various neurosteroids. Recently, we found that the brain of newts actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. Interestingly, this novel neurosteroid acts as a neuronal modulator to stimulate locomotor activity in male newts. Locomotor activity of vertebrates changes after acute stress and the dorsomedial hypothalamus (DMH) coordinates physiological and behavioral responses to stress, but the molecular mechanisms underlying this process are poorly understood. In this study, we hypothesized that acute stress increases 7alpha-hydroxypregnenolone synthesis to modulate locomotor activity. Here, using the newt, a wild animal which serves as an excellent model to investigate neurosteroid actions under stress, we show that 7alpha-hydroxypregnenolone mediates corticosterone action to increase locomotor activity under stress through serotonergic system. Acute stress increased 7alpha-hydroxypregnenolone synthesis in the brain through corticosterone action. Glucocorticoid receptor was identified in DMH neurons expressing cytochrome P4507alpha, the steroidogenic enzyme of 7alpha-hydroxypregnenolone synthesis. Finally, we clarified that 7alpha-hydroxypregnenolone stimulates serotonin concentrations in the diencephalon including the DMH. This is the first elucidation of molecular mechanisms in the brain underlying behavioral changes during stress in any vertebrate class.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan to KT and a Japan Society for the Promotion of Science (JSPS) – Institut National de la Santé de la Recherche Médicale (INSERM) exchange program to KT and HV.
Keywords:
7alpha-Hydroxypregnenolone,
acute stress,
Corticosterone,
Neurosteroids,
newt brain,
Serotonin
Conference:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology, Ann Arbor, United States, 11 Jul - 13 Jul, 2011.
Presentation Type:
Poster
Topic:
Stress
Citation:
Haraguchi
S,
Koyama
T,
Hasunuma
I,
Okuyama
S,
Kikuyama
S,
Do-Rego
J,
Vaudry
H and
Tsutsui
K
(2011). 7alpha-HYDROXYPREGNENOLONE ACTS AS A SEROTONIN-INDUCING FACTOR TO INCREASE LOCOMOTOR ACTIVITY VIA CORTICOSTERONE ACTION UNDER STRESS.
Front. Endocrinol.
Conference Abstract:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology.
doi: 10.3389/conf.fendo.2011.03.00015
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Received:
06 Jul 2011;
Published Online:
09 Aug 2011.
*
Correspondence:
Prof. Kazuyoshi Tsutsui, Waseda University, Department of Biology, Tokyo, 162-8480, Japan, k-tsutsui@waseda.jp