Studies on ovarian-hypothalamic-pituitary interactions during reproductive aging in C57BL/6J mice

Studies on the reproductive senescence of C57BL/6J female mice from this and other laboratories are reviewed. Although the ovary ages irreversibly as monitored by the loss of primary oocytes and follicles, at ages (9-12 mo) when estrous cycles lengthen and fertility decreases strikingly, normal numbers of ova are still produced. Analysis of hormone output reveals impairments in the spontaneous and experimentally induced LH surges of aging mice which imply altered transduction of the estradiol signal triggering the release of LHRH. The loci responsible for this failure to transduce the estradiol signal are unknown, but could involve hypothalamic monoaminergic transmission as well as the LHRH neurons. Morphologic studies on C57BL/6J mice and other rodents indicate degenerative changes in arcuate neuronal processes with concommitant glial hyperactivity and reduced density of LHRH containing fibres. Recent evidence indicates that exposure to estradiol is one cause of the hypothalamic changes associated with reproductive senescence. Age changes in the regulation of the LH surge are delayed by long-term ovariectomy, and accelerated by short-term exposure to high levels of estradiol. These results are paralleled by morphologic changes in the arcuate nucleus. Taken together, the available data suggest that there is a cumulative impact of steroids on hypothalamic loci critical to the LH surge which is independent of chronologic age.