The striated bulbocavernosus (BC) muscles of the rodent perineum are innervated by motoneurons in the spinal nucleus of the bulbocavernosus (SNB). In adulthood, the BC muscles are present in males only. However, newborn female rats have BC muscles and SNB cells have made both anatomical and functional contact with them. Nevertheless, both SNB motoneurons and BC muscles will degenerate in females unless androgens are administered perinatally. There is evidence that such androgen treatment acts primarily on the BC muscles themselves, since the muscles are spared by androgen after the loss of supraspinal neural afferents or even the entire lumbosacral spinal cord. Two experiments are proposed to confirm or refute the target muscles as the primary site of androgen action upon the SNB system. One experiment will attempt to spare montoneurons which are themselves genetically incapable of responding to androgen. The second experiment will attempt to masculinize the SNB system by providing androgen responsive BC muscles transplants to androgen-insensitive newborn males. The possiblity that BC muscles produce proteins which are retrogradely transported by developing SNB cells will be investigated by amino acid autoradiography. Perinatal treatment with the steroid DHTP can alter the final spinal location of SNB cells as determined by previous retrograde tracing studies. There is suggestive evidence that DHTP accomplishes this abnormal spinal location by affecting the migration of motoneurons. Two experiments will test this hypothesis. Finally, the sexually dimorphic character of motoneuronal groups innervating perineal muscles seems to be common in mammals, since the homologue to the SNB, Onuf's nucleus, has more cells in males than in females in both dogs and humans. Furthermore, the number of Onuf's motoneurons is altered by perinatal androgen in dogs. We will conduct androgen autoradiography to determine whether motoneurons in Onuf's nucleus accumulate androgen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019790-06
Application #
3399882
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-07-01
Project End
1990-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
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