The proposed project will study the development of a neuromuscular system that is present in male, but not female rats. The motoneurons of this system form the spinal nucleus of the bulbocavernosus (SNB) and innervate the perineal muscles bulbocavernosus (BC) and levator ani (LA). The BC/LA muscles are present in both sexes at birth, but disappear in females after birth. Androgen treatment of females around the time of birth causes the muscles and the SNB to persist. This project will study the androgen dependent development of the SNB system. The ontogeny of contact between SNB cells and BC/LA muscles will be monitored by staining muscle endplates, stimulating the efferent nerve an injecting retrogradely transported horseradish peroxidase (HRP). The time of neuromuscular innervation will be compared with the critical periods for androgenic masculinization of SNB morphology. A longitudinal study will measure the effect of perinatal hormonal manipulations upon the innervation process. The project will also examine the role of supraspinal afferents in the development of the SNB system. The ontogeny of androgen accumulation by SNB cells will be determined using autoradiographic techniques. Prenatal treatment of females with a particular androgen results in the independent masculinization of the muscles but not the SNB. The muscles of these females will be injected with HRP to determine whether their condition results from an abnormal motoneuron to muscle projection. These investigations of the mechanisms which determine the number and size of neurons present in adulthood may contribute to the understanding of neural development and neuromuscular interactions. The spinal motoneurons of male rats accumulate hormone more often and more heavily than those of females, following injection of testosterone. Autoradiograms from perinatally treated rats will be examined to determine whether the sex difference in hormone accumulation is due to androgen action during development. The development of such sex differences in hormone accumulation may represent an important dimension of the sexual differentiation of the nervous system. The final experiment will test the hypothesis that androgens exert their anabolic effects on muscle weight and composition by acting upon the motoneurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019790-03
Application #
3399880
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704