Discovery of novel neurohormones and their mode of action and functional significance

Kazuyoshi Tsutsui, ”Discovery of novel neurohormones and their mode of action and functional significance”

Probing undiscovered neurohormones, such as neuropeptides and neurosteroids, that play important roles in the regulation of brain function in vertebrates is essential for the progress of "Neuroendocrinology" and "Neurobiology". To open the door to a new research field in "Neuroendocrinology" and "Neurobiology", my main research over the past decade has been focusing on the discovery of novel neurohormones and the demonstration of their mode of action and functional significance.  
Our studies over the past decade by focusing on novel neuropeptides and neurosteroids have uncovered several “firsts” and contributed to the progress of "Neuroendocrinology" and "Neurobiology".
In 1995, we first found de novo neurosteroidogenesis in the avian brain from cholesterol and subsequently demonstrated the biosynthetic pathway of neurosteroids in birds. We also discovered that the Purkinje cell, an important brain neuron, is a major site for neurosteroid formation in the brain of a variety of vertebrates. This discovery has allowed deeper insights into neuronal neurosteroid formation and diverse actions of neurosteroids have become clear by our studies using the Purkinje cell as an excellent cellular model, which is known to play an important role in memory and learning processes. The promotion of neuronal growth, spinogenesis and synaptogenesis and the modulation of synaptic neurotransmission by neurosteroids have been demonstrated. We have further identified 7α-hydroxypregnenolone as a novel bioactive neurosteroid in the brain of vertebrates . 7α-Hydroxypregnenolone acts as a key factor for induction of locomotor activity of vertebrates and melatonin regulates synthesis of this neurosteroid, thus inducing diurnal locomotor changes of vertebrates.
   In 2000, we discovered GnIH as a novel hypothalamic neuropeptide in birds. The neuropeptide gonadotropin-releasing hormone is known to be the primary factor responsible for the hypothalamic control of gonadotropin secretion. However, an inhibitory neuropeptide of gonadotropin secretion was, until recently, unknown in any vertebrate. Subsequently, we demonstrated that GnIH inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in birds. It is also becoming clear that a similar gonadotropin-inhibitory system is present in mammals including primates and humans. Thus, the discovery of GnIH has opened a new research field in reproductive neuroendocrinology from a novel standpoint.