CORTICOTROPIN-RELEASING HORMONE AND RELATED NEUROPEPTIDES STIMULATE NEUROSTEROID BIOSYNTHESIS IN THE FROG BRAIN
Jean-Luc
Do-Rego1*,
Jae Young
Seong2,
Shogo
Haraguchi3,
Mi-Jin
Moon2,
David
Vaudry4,
Teppei
Koyama3,
Itaru
Hasunuma3,
Robert
J.
Denver5,
Georges
Pelletier6,
Kazuyoshi
Tsutsui3 and
Hubert
Vaudry1, 4*
-
1
INSERM, University of Rouen, France
-
2
Korea University, Republic of Korea
-
3
Waseda University, Department of Biology, Japan
-
4
INSERM U982, University of Rouen, France
-
5
The University of Michigan, Department of Molecular, Cellular and Developmental Biology (MCDB), Department of Ecology and Evolutionary Biology (EEB), United States
-
6
Laval University Hospital Research Center, Canada
Neurosteroids are known to exert a wide variety of neuroendocrine, behavioral and pathophysiological activities. In particular, certain neurosteroids mimic the anxiogenic, depressive-like and anorexigenic effects of corticotropin-releasing hormone (CRH) and its paralogs urocortins (UCNs). However, the possible role of CRH and UCNs in the regulation of neurosteroid production has never been reported. We have thus investigated the possible effect of CRH and related peptides on the biosynthesis of neurosteroids in the brain of the frog Rana esculenta. Double immunohistochemical labeling of frog brain sections, showed that 3beta-hydroxysteroid dehydrogenase (3beta-HSD)-, cytochrome P450C17 (P450C17)- and 5alpha-reductase (5alpha-R)-containing neurons are often apposed by CRH-immunoreactive fibers. 3beta-HSD- and 5alpha-R-expressing neurons are also surrounded by UCN-positive processes. In addition, the diencephalic regions where most 3beta-HSD-, P450C17- and 5alpha-R-positive neurons are located are enriched with CRH receptor-like immunoreactivity. Exposure of frog hypothalamic explants to graded concentrations of CRH or urocortin-I (UCN-I) (10-12 - 10-5 M) produced a dose-dependent increase in the formation of progesterone, 17-hydroxypregnenolone, dehydroepiandrosterone and allopregnanolone. The stimulatory effect of CRH and UCN-I was mimicked by sauvagine and urotensin-I. Time-course experiments revealed that a 15-min incubation of hypothalamic explants with CRH or UCN-I was sufficient to induce a robust increase in neurosteroid production and that the maximum effect was observed after a 1-h exposure to CRH or a 2-h exposure to UCN-I, suggesting that CRH and UCN-I activate steroidogenic enzymes at a post-translational level. In conclusion, the present study provides the first evidence that, in the brain of vertebrates, some of the neurophysiological and behavioral effects of CRH and related peptides may be mediated via the regulation of neurosteroid production.
Acknowledgements
Supported by INSERM, the Regional Platform for Cell Imaging (PRIMACEN), a France-Japan exchange program (INSERM-JSPS), a France-Korean exchange program (STAR), a France-Québec exchange program (INSERM-FRSQ), and the Région Haute-Normandie.
Keywords:
Brain,
CRH,
Frog,
Neurosteroids,
stress
Conference:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology, Ann Arbor, United States, 11 Jul - 13 Jul, 2011.
Presentation Type:
Oral Presentation
Topic:
Abstracts
Citation:
Do-Rego
J,
Seong
J,
Haraguchi
S,
Moon
M,
Vaudry
D,
Koyama
T,
Hasunuma
I,
Denver
RJ,
Pelletier
G,
Tsutsui
K and
Vaudry
H
(2011). CORTICOTROPIN-RELEASING HORMONE AND RELATED NEUROPEPTIDES STIMULATE NEUROSTEROID BIOSYNTHESIS IN THE FROG BRAIN.
Front. Endocrinol.
Conference Abstract:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology.
doi: 10.3389/conf.fendo.2011.03.00010
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Received:
20 Jul 2011;
Published Online:
09 Aug 2011.
*
Correspondence:
Dr. Jean-Luc Do-Rego, INSERM, University of Rouen, Mont-Saint-Aignan, 76821, France, Jean-Luc.Do-Rego@univ-rouen.fr
Prof. Hubert Vaudry, INSERM, University of Rouen, Mont-Saint-Aignan, 76821, France, hubert.vaudry@univ-rouen.fr