Neuroendocrine influences on aging of the female reproductive system

Many changes in neural, pituitary and ovarian function contribute to the aging of the female reproductive system. Clearly, the diminishing number of ovarian oocytes influences when reproductive cycles cease in aging animals. However, a growing body of evidence demonstrates that changes in neurotransmitter and neuroendocrine functions play major roles in the cascade of events leading to age-related acyclicity. In laboratory rats, changes in the pattern of neurotransmitter and gonadotropin releasing hormone (GnRH) release occur during the initial stages of reproductive aging and may alter the normal pattern of follicular development and steroid secretion during middle-age. In this review, we discuss findings that suggest that the mechanisms that regulate reproductive aging in humans and rats may not differ as much as is generally believed. The aging female reproductive system is an excellent model system in which to assess the processes that regulate aging of the brain. Since female reproductive function declines early during the lifespan of many species, investigators can examine aging of this system in the absence of agerelated changes in other endocrine and other physiological systems. Thus, it should be possible to differentiate between primary age-related alterations in the reproductive system and reproductive changes that occur secondary to age-related degenerative and pathological changes in other physiological systems that ultimately feed back to affect fertility. The use of modern neurobiological and molecular methods to assess neural function within small brain regions should deepen our understanding of how changing neuroendocrine events contribute to female reproductive aging.