The role of target muscles in the expression of calcitonin gene-related peptide mRNA in the spinal nucleus of the bulbocavernosus

Abstract

Previous studies have shown that calcitonin gene-related peptide (CGRP) mRNA steady-state levels and CGRP immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus (SNB) are inversely related to the gonadal steroid environment in male rats. Since both the SNB motoneurons and their target muscles, the bulbocavernosus and the levator ani, are steroid sensitive, gonadal steroids may act at either site to regulate CGRP expression. In the present study, we tested the hypothesis that gonadal steroids influence CGRP expression in SNB motoneurons through their effects on the bulbocavernosus and levator ani muscles. We determined the levels of α-CGRP mRNA and immunoreactive CGRP in SNB motoneurons of adult male rats following injection of the bulbocavernosus with muscle extracts from bulbocavernosus/levator ani of castrated rats, paralysis of the bulbocavernosus or pudendal nerve cuts. Following injection of the bulbocavernosus/levator ani with extracts from castrated rats, the level of CGRP expression and the number of SNB motoneurons with α-CGRP message were increased. These studies suggest that the bulbocavernosus/levator ani muscles from castrated rats produce a factor that increases levels of CGRP. Injections of extract prepared from the bulbocavernosus and levator ani muscles of gonadally intact rats did not change the expression of α-CGRP mRNA in the SNB. Paralysis of the bulbocavernosus/levator ani with a local anesthetic increased the number of SNB motoneurons expressing α-CGRP mRNA and CGRP immunoreactive neurons. To determine whether nerve damage accounted for the observed effects following injection of anesthetic, the pudendal nerves were cut bilaterally. This produced an elevation of the levels of α-CGRP mRNA in SNB motoneurons but did not change the number of CGRP expressing neurons. Our results suggest that nerve damage increases α-CGRP mRNA levels and that soluble factor(s) derived from the bulbocavernosus/levator ani muscle stimulate the expression of α-CGRP mRNA and CGRP immunoreactivity in the SNB.