Genetic abnormalities and male infertility. A comprehensive review

We have previously observed that ciliary neurotrophic factor (CNTF) can prevent the degeneration of androgen-sensitive perineal motoneurons and their target muscles, the bulbocavernosus and levator ani (BC/LA), in perinatal female rats. Response to CNTF is dependent on the expression of the alpha component of the CNTF receptor (CNTFRalpha). In the present study, we examined the developmental profile and androgen regulation of CNTFRalpha gene expression in BC/LA muscle, thigh muscle, and lumbosacral spinal cord. CNTFRalpha mRNA was abundantly expressed in the BC/LA and thigh around the time of birth; expression declined progressively after birth and remained low into adulthood. In contrast, CNTFRalpha message remained high in the lumbosacral spinal cord throughout development. Androgen regulation of CNTFRalpha expression was examined in prenatal animals by administering the androgen receptor blocker hydroxyflutamide from embryonic days E18 through E21. Four days of androgen deprivation caused a significant up-regulation of CNTFRalpha mRNA in the BC/LA, thigh, and spinal cord of male fetuses. After castration in adulthood, CNTFRalpha expression in the BC/LA transiently increased, then decreased below control levels. Expression of CNTFRalpha in thigh muscles and the lumbosacral spinal cord was not affected by adult castration. Thus, the perineal muscles and motoneurons are potential sites of direct CNTF action, and expression of the CNTFRalpha gene is modulated by androgen, especially in the androgen-sensitive perineal muscles. Transient up-regulation of CNTFRalpha following castration or androgen receptor blockade may represent a protective response designed to counteract the muscle atrophy normally induced by androgen withdrawal.