Aging in the female reproductive system of rats produces disturbances in the timing of LH surges. In young rats, the temporal pattern of cyclic LH secretion is influenced in part, by a circadian rhythm in serotonin (5HT) metabolism within the suprachiasmatic nucleus (SCN). As female rats age, the 5HT circadian rhythm degrades, altering the quantity and pattern of LH secretion and causing functional dysynchrony in the reproductive neuroendocrine axis. Thus, neurochemical changes affecting rhythmic patterns of 5HT metabolism in SCN are fundamental to the mechanism of aging in the female reproductive system. This project will investigate factors having the potential to alter patterns of SCN:5HT during aging. These include changes in activity and turnover of synthetic and degradative enzymes, glucose utilization, cyclic nucleotides, protein synthesis, axonal transport and/or structural degeneration in serotoninergic neurons.
The specific aims of the project are to determine activities of tryptophan hydroxylase, monoamine oxidase 5-hydroxytryptophan decarboxylase and dihydropteridine reductase by radioenzymatic analyses, in SCN, as well as in raphe nuclei and retina, which contain neurons that project to SCN and affect 5HT metabolism. Since glucose provides essential energy requirements for timed biological reactions, patterns of carbohydrate metabolism related to 5HT synthesis in SCN will be monitored during aging. Cyclic adenosine monophosphate also influences the activity and/or synthesis of 5HT; therefore, patterns of this cyclic nucleotide in SCN and other relevant sites will be monitored. Since protein synthesis is involved in the regulation of reproductive rhythmicity, it will also be monitored during senescence, and the effects of locally applied antibiotics on LH and 5HT circadian rhythms will be tested. Finally, the facilitatory effect of 5HT on LH surges may be lost during aging following degeneration of 5HT axon terminals in SCN. Thus, axonal transport from raphe and retina to SCN will be tested along with 5HT synaptic activity in SCN, at various stages of the reproductive life span. In an attempt to reverse structural deficiencies and restore cyclic reproductive function, fetal tissue will be transplanted to SCN and/or raphe of old rats. Collectively, these studies make a systematic attempt to understand one aspect of the mechanism for aging; the related to changing patterns of 5HT metabolism in SCN, and its role in age-related loss of temporal organization in the female reproductive system.
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