[Frontiers in Bioscience 17, 996-1019, January 1, 2012] 996 Rapid signaling of steroid hormones in the vertebrate nervous system Hirotaka Sakamoto 1 , Hideya Takahashi 2 , Ken-Ichi Matsuda 3 , Mayumi Nishi 4 , Keiko Takanami 3 , Maho Ogoshi 1 , Tatsuya Sakamoto 1 , Mitsuhiro Kawata 3 1 Ushimado Marine Laboratory, Graduate School of Natural Science and Technology, Okayama University, Kashino, Ushimado, Setouchi, Okayama 701-4303, Japan, 2 Department of Environmental Science, Faculty of Science, Niigata University, Ikarashi, Niigata 950-2181, Japan, 3 Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi- Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan, 4 Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Nara 634-8521, Japan TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Sexsteroids 3.1. Estrogens 3.2. Progestins 3.3. Androgens 4. Corticoids 4.1. Glucocorticoids 4.2. Mineralocorticoids 4.2.1. Mammals 4.2.2. Fish 5. Neurosteroids 6. Conclusion 7. Acknowledgment 8. References 1. ABSTRACT Steroid hormones easily cross the blood–brain barrier because of their physicochemical lipid solubility. The hormones act through nuclear receptor-mediated mechanisms and modulate gene transcription. In contrast to their genomic actions, the non-genomic rapid action of steroid hormones, acting via various types of membrane- associated receptors, reveals pharmacological properties that are distinct from the actions of the intracellular nuclear receptors. As a result, non-genomic rapid actions have gained increased scientific interest. However, insight into the phylogenic and/or comparative actions of steroids in the brain is still poorly understood. In this review, we summarize recent findings concerning the rapid, non- genomic signaling of steroid hormones in the vertebrate central nervous system, and we discuss (using a comparative view from fish to mammals) recently published data regarding the mechanism underlying physiology and behavior. 2. INTRODUCTION Steroids are a large family of chemical substances comprising many hormones and vitamins built on cyclopentanoperhydrophenanthrene, a tetracyclic nucleus (i.e., steroid skeleton) (see Figure 1) (1). Cholesterol is the precursor of the five major classes of steroid hormones: estrogens, progestins, androgens, glucocorticoids and mineralocorticoids in vivo (Figure 1) (1, 2). In vertebrates, steroid hormones supplied by the peripheral endocrine glands regulate numerous important functions not only in the peripheral organs but also in the central nervous system (CNS) during development and this regulation persists into adulthood (2-7). Peripheral steroid hormones have a small molecular weight (less than 400) and easily cross the blood-brain barrier because of their physicochemical lipid solubility. They act directly on neuronal tissues through nuclear receptor-mediated mechanisms and modulate nuclear transcriptions. Thus, the steroid hormones trigger genomic actions that result in