Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 2. Discovery of neurosteroids and pineal neurosteroids.
Bargmann-Scharrer's discovery of "neurosecretion" in the first half of the 20th century has since matured into the scientific discipline of neuroendocrinology. Identification of novel neurohormones, such as neuropeptides and neurosteroids, is essential for the progress of neuroendocrinology. Our studies over the past two decades have significantly broadened the horizons of this field of research by identifying novel neuropeptides and neurosteroids in vertebrates that have opened new lines of scientific investigation in neuroendocrinology. We have established de novo synthesis and functions of neurosteroids in the brain of various vertebrates. Recently, we discovered 7α-hydroxypregnenolone (7α-OH PREG), a novel bioactive neurosteroid that acts as a key regulator for inducing locomotor behavior by means of the dopaminergic system. We further discovered that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol (CHOL). The pineal gland secretes 7α-OH PREG and 3α,5α-tetrahydroprogesterone (3α,5α-THP; allopregnanolone) that are involved in locomotor rhythms and neuronal survival, respectively. Subsequently, we have demonstrated their mode of action and functional significance. This review summarizes the discovery of these novel neurosteroids and its contribution to the progress of neuroendocrinology.
Laboratory of Integrative Brain Sciences, Department of Biology and Center for Medical Life Science, Waseda University, Tokyo 162-8480, Japan. Electronic address: k-tsutsui@waseda.jp.
Kazuyoshi
K
Tsutsui
Laboratory of Integrative Brain Sciences, Department of Biology and Center for Medical Life Science, Waseda University, Tokyo 162-8480, Japan.
Shogo
S
Haraguchi
D006907:17-alpha-Hydroxypregnenolone / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D006801:Humans; D009043:Motor Activity / Q000502:physiology; D009452:Neuroendocrinology; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010870:Pineal Gland / Q000378:metabolism*
C495856:7-hydroxypregnenolone; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D006907:17-alpha-Hydroxypregnenolone
3α,5α-Tetrahydroprogesterone (3α,5α-THP); 7α-Hydroxypregnenolone (7α-OH PREG); Brain; Locomotor behavior; Neuronal survival; Pineal gland