ANABOLIC-ANDROGENIC STEROID-INDUCED ALTERATIONS IN CHOLINE-ACETYLTRANSFERASE MESSENGER-RNA LEVELS OF SPINAL-CORD MOTONEURONS IN THE MALE-RAT

The effect of chronic supraphysiological doses of anabolic-androgenic steroids, such as those illegally used by recreational, amateur and pr ofessional athletes to increase muscle mass and strength, on motoneuro ns has not been established. The choline acetyltransferase activity le vels of perineal muscles in the male rat are modulated by plasma testo sterone levels. These muscles are innervated by the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus. Since the p rimary source of choline acetyltransferase in muscle is motoneuronal, testosterone may modulate perineal muscle choline acetyltransferase ac tivity by regulating choline acetyltransferase messenger RNA levels in motoneurons. The purpose of this study was to determine if choline ac etyltransferase messenger RNA levels in cervical and lumbar spinal mot oneurons are affected by chronic (four weeks) changes of plasma testos terone levels in the adult male rat. Using in situ hybridization, chol ine acetyltransferase messenger RNA levels were analysed in four motor columns: the spinal nucleus of the bulbocavernosus, the retrodorsal l ateral nucleus of the lumbar spinal cord, and the lateral motor column s of the cervical and lumbar spinal cords. Chronic exposure to supraph ysiological levels of testosterone (five- to ten-times physiologic lev els) significantly increased choline acetyltransferase messenger RNA i n all four motor columns. Subsequent to castration, choline acetyltran sferase messenger RNA levels decreased in motoneurons of the spinal nu cleus of the bulbocavernosus and the retrodorsal lateral nucleus. This observation suggests that the decrease in choline acetyltransferase a ctivity levels of muscles innervated by spinal nucleus of the bulbocav ernosus motoneurons may be due to changes in choline acetyltransferase protein levels. Indeed, testosterone replacement therapy of castrated males prevented the decline of choline acetyltransferase messenger RN A levels in motoneurons. The results of this study demonstrate that an abolic-androgenic steroids can affect the levels of specific messenger RNAs in motoneuron populations throughout the spinal cord suggesting that motoneuronal characteristics are modulated by circulating anaboli c-androgenic steroid levels regardless of the purported ''androgen sen sitivity'' of the specific neuromuscular system. (C) 1997 IBRO.