| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Motoneurons of the spinal nucleus of the bulbocavernosus (SNB) of male rats innervate the perineal striated muscles bulbocavernosus and levator ani that attach to the penis.
They contain androgen receptors (AR) and have an important role in copulatory behavior, which is sensitive to alterations in circulating levels of androgen. It is well known that androgen regulates gen expression first by binding to AR and then by interaction of androgen-AR complex with androgen response elements on the DNA that act as transcriptional factors. Recently it has been shown that there are nuclear receptor coregulators are coactivators or corepressors that are required by nuclear receptors for efficient transcriptional regulation. To clarify regulatory mechanisms of coregulators, we examined whether androgen regulates expression of coregulators such as cyclic AMP response element-binding protein (CREB), CREB-binding protein (CBP) and steroid receptor-coactivator-1 (SRC-1) in the SNB motoneurons in young adult male rats (2 months of age) by immunohistochemistry. In intact male rats, intense CREB, CBP and SRC-1 immunoreactivity were confined to the cell nucleus, but not to the nucleolus of SNB motoneurons. Androgen withdrawal by castration did not induce any changes in expression of these coregulators. These results indicate that androgen may not participate in expression of these coregulators in SNB motoneurons. On the other hand, in aged animals (22 months of age), the intensity of CREB immunoreactivity in the nuclei, number of CREB immunopositive nuclei of the SNB motoneurons and plasma levels of androgen in aged animals were significantly reduced as compared with young ones. A marked decline in expression of CREB in the aged SNB motoneurons suggest alternation of c-AMP-mediated regulation of gene expression in the SNB system with advancing age. A decline in plasma levels of androgen may not be involved in the phenomenon.
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