TRENDS IN COMPARATIVE ENDOCRINOLOGY AND NEUROBIOLOGY Diurnal Changes in the Synthesis of the Neurosteroid 7α -Hydroxypregnenolone Stimulating Locomotor Activity in Newts Teppei Koyama, a Shogo Haraguchi, a Hubert Vaudry, b and Kazuyoshi Tsutsui a a Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Tokyo, Japan b Institut National de la Sant´ e et de la Recherche M´ edicale U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research, University of Rouen, Mont-Saint-Aignan, France We recently identified 7α-hydroxypregnenolone as a novel amphibian neurosteroid stim- ulating locomotor activity in newts. Because male newts show marked diurnal changes in locomotor activity, we hypothesized that 7α-hydroxypregnenolone may be a key fac- tor for the induction of diurnal changes in locomotor activity in male newts. In this study, we found diurnal changes in 7α-hydroxypregnenolone synthesis in the brain of male newts, which paralleled locomotor activity. Interestingly, the production of 7α- hydroxypregnenolone in the male newt brain increased during the dark phase when locomotor activity of males was high. Key words: neurosteroids; 7α-hydroxypregnenolone; locomotor activity; diurnal chan- ges; newts Introduction A ubiquitous property of vertebrates is fluc- tuation of locomotor activity over the 24-h cir- cadian cycle. 1 However, molecular mechanisms for the regulation of diurnal locomotor rhythms are poorly understood in vertebrates. The brain has traditionally been consid- ered to be a target site of peripheral steroid hormones. However, it is becoming clear that steroids can be synthesized de novo by brain and the peripheral nervous systems. Such steroids are called “neurosteroids,” and de novo neuro- steroidogenesis from cholesterol is a conserved property of vertebrate brains (for reviews see Refs. 2–7). Our studies over the past decade have demonstrated that the brain possesses sev- Address for correspondence: Kazuyoshi Tsutsui, PhD, Professor, Lab- oratory of Integrative Brain Sciences, Department of Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162–8480, Japan. Voice: +81 3 5369 7311; fax: +81 3 5369 7302. k-tsutsui@waseda.jp eral kinds of steroidogenic enzymes and pro- duces a variety of neurosteroids in nonmam- malian vertebrates, such as birds, amphibians and fish (for reviews see Refs. 4–7). However, the biosynthetic pathway of neurosteroids in nonmammals as well as in mammals may still be incompletely mapped out (for a review see Ref. 8). We recently demonstrated that the newt brain actively produces 7α-hydroxy- pregnenolone, a novel amphibian neuros- teroid, from pregnenolone. 9 We further demonstrated that 7α-hydroxypregnenolone stimulates locomotor activity of newts by means of the dopaminergic system. 9 It is known that breeding newts show diur- nal variations in locomotor activity. 10 Because 7α-hydroxypregnenolone acts as a novel neu- ronal activator to stimulate locomotor activity of breeding newts, 9 we hypothesized that this neurosteroid may be a key factor for the induc- tion of diurnal changes in locomotor activity Trends in Comparative Endocrinology and Neurobiology: Ann. N.Y. Acad. Sci. 1163: 444–447 (2009). doi: 10.1111/j.1749-6632.2008.03622.x C  2009 New York Academy of Sciences. 444