IDENTIFICATION, MODE OF ACTION AND FUNCTIONAL SIGNIFICANCE OF 7alpha-HYDROXYPREGNENOLONE, A NEW KEY REGULATOR OF AMPHIBIAN LOCOMOTION
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1
Waseda University, Department of Biology, Japan
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2
University of Rouen, INSERM U982, European Institute for Peptide Research, France
The brain has traditionally been considered as a target site for peripheral steroid hormones. In addition to this classical concept, it is now established that steroids can be synthesized de novo in the central and peripheral nervous systems. Such steroids are called “neurosteroids”. Amphibians have served as excellent animal models for investigating neurosteroid biosynthesis. In fact, our studies over the past two decades have demonstrated that the brain of amphibians possesses several kinds of steroidogenic enzymes and produces a variety of neurosteroids. However, the biosynthetic pathways of neurosteroids in the brain were still incompletely elucidated in amphibians as well as in other vertebrates. Recently, we found that the newt brain actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid, from pregnenolone. Importantly, 7alpha-hydroxypregnenolone acts as a novel neuronal modulator to stimulate locomotor activity of newts through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone, we demonstrated diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis in the brain in parallel with changes in locomotor activity of newts. We further elucidated the mechanisms regulating diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis. Interestingly, melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. On the other hand, prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and induces seasonal locomotor changes. Thus, the discovery of 7alpha-hydroxypregnenolone and its role in mediating the actions of melatonin and prolactin have improved our understanding of the molecular mechanisms underlying diurnal and seasonal changes in locomotor activity in amphibians.
Keywords:
7alpha-Hydroxypregnenolone,
diurnal changes,
locomotor activity,
Melatonin,
Neurosteroids,
newt brain,
Prolactin,
seasonal changes
Conference:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology, Ann Arbor, United States, 11 Jul - 13 Jul, 2011.
Presentation Type:
Plenary
Topic:
Brain and behavior
Citation:
Tsutsui
K,
Haraguchi
S,
Matsunaga
M,
Koyama
T,
Hasunuma
I,
Do-Rego
J and
Vaudry
H
(2011). IDENTIFICATION, MODE OF ACTION AND FUNCTIONAL SIGNIFICANCE OF 7alpha-HYDROXYPREGNENOLONE, A NEW KEY REGULATOR OF AMPHIBIAN LOCOMOTION.
Front. Endocrinol.
Conference Abstract:
ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology.
doi: 10.3389/conf.fendo.2011.03.00044
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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