Abstract
The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone.
Highlights
We discovered that Purkinje cells, a major neuronal population actively produce a variety of neurosteroids de novo from cholesterol in the brain of various vertebrates (Tsutsui and Yamazaki, 1995; Usui et al, 1995; Ukena et al, 1998, 1999; Takase et al, 1999; Matsunaga et al, 2001; Sakamoto et al, 2001a,b, 2003a; Agís-Balboa et al, 2006, 2007)
We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ actively producing a variety of neurosteroids de novo from cholesterol (Hatori et al, 2011; Haraguchi et al, 2012b) (Figure 1)
This is a paradigm shift of neurosteroid formation, because it was accepted that neurosteroids are synthesized only in glial cells and neurons which are located in the brain and peripheral nervous systems for the past 30 years
Summary
We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. We have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development.
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