One impairment in the function of neuroendocrine cells in aging animals appears to be a deficit in neurosecretion. Further, it is thought that this deficit results, in part, from declining activity of neurons that is characteristic of aging animals. However, relatively little is known about the relationship between neural activity and biosynthesis of neuropeptides. Biosynthesis of several neuropeptides involves initial synthesis of larger molecular weight precursors that are subsequently modified to yield smaller molecular weight peptides which are physiologically active. We propose to examine products of biosynthesis and maturation of a neuropeptide, luteinizing hormone releasing hormone (LHRH). Age-related alterations in the function of LHRH neurons are thought to significantly contribute to the reproductive decline apparent in aging rodents. We propose to, first, identify molecular weight species of LHRH and, secondly, to quantify their occurrence in extracts from the preoptic/hypothalamic area of young and aging rats. To accomplish this we will use a combination of techniques including: sizing columns, reverse phase high performance liquid chromatography and radioimmunoassay. Since it is not known how gonadal steroids influence the biosynthesis and/or post-translation of LHRH, rats will be sacrificed in several hormonal conditions and every attempt will be made to equalize hormonal environments of young and old animals. These studies constitute a novel and unique approach to conceptualize the intraneuronal balance of biosynthesis and maturation of hypothalamic neuropeptides in aging animals.
