This research project seeks to extend our previous studies of hormonal control of neuronal development and function, which have been based on the Fundamental Hypothesis that gonadal steroids regulate the growth and development, and adult functional adaptability of peripheral sympathetic and parasympathetic neurons. Observations garnered steroids regulate neuropeptides in autonomic ganglia; gonadal steroids regulate neurotrophic factors in target organs of pelvic autonomic ganglia; and gonadal regulate the development of target organ innervation by autonomic neurons. The overall theme of these efforts is to establish a better understanding of the spectrum of hormonal influences on neuronal systems, and the mechanisms by which these steroid effects are mediated. The major questions to be asked include: 1) Does testosterone regulate the levels of mRNA for tyrosine hydroxylase (T-OH), T-OH enzyme protein, and T-OH activity in a specific manner? Will T-OH in situ hybridization permit identification of hormonal response patterns restricted to specific neurons in ganglia? Do hormones interact directly with the neuron? 2) Do hormones regulate neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in pelvic ganglia? These two peptides are integrally involved in reproductive and excretory functions. 3) Are trophic molecules such as nerve growth factor (NGF) influenced by gonadal steroids, and do changes in the NGF receptor occur with hormonal pertubation? Do hormones exert their effects via target organs and the production of such trophic molecules? 4) Is the ability of the nerve to innervate target organs regulated by steroids? These studies will draw on multidisciplinary techniques including neurochemical, pharmacological, molecular biological, and tissue culture methods. Together these experiments should provide a detailed examination of the possible mechanisms by which steroids influence neuronal systems during development and adulthood. Thus, in a more general sense these studies should be relevant to issues of how the environmental milieu might influence the developing neuron and result in ontogenetic errors and defects. Since steroids may influence the aging process per se, our studies may have relevance from birth to senescence. Accordingly, the clinical relevance of these observation might include new understandings of birth defects, neurodegenerative disorders, neuroplasticity, and aging.
