Development and regeneration of motor systems under the influence of ACTH peptides.

ACTH peptides exert quantitative and qualitative influences on the formation and maturation of motor units in developing and regenerating neuromuscular systems. ACTH 4-10, administered daily (10 micrograms/kg. s.c.) from the day of birth, accelerated the rate at which muscle strength developed in the immature rat, the effect of this peptide being most marked in animals 11-15 days old. A similar increase in grasping time occurred in ACTH 4-10 treated animals, indicating that the peptide affects neuronal maturation at a time in development when organization and maturation of the neuromuscular system is most active. The synthetic analogue of ACTH 4-9 (Org 2766), administered in the same dosage, had little effect on these parameters, indicating a differential sensitivity to these similar peptides. Elevated circulating titers of ACTH, whether exogenous (0.2 U ACTH 1-39 IP daily), or endogenous (adrenalectomy), stimulated the formation of more functional motor units, as indicated by increased amplitude of muscle action potentials and tetanic tension following nerve stimulation. ACTH appears to favor the recovery of high threshold, small-size motor units. Fine control of muscle function in peptide-treated animals is partially restored, as indicated by the return of stepwise recruitment to an extent not seen in the reinnervated, saline-treated controls.