Estrogen, the ovary, and neurotransmitters: Factors associated with aging

Our studies in the C57BL/6J mouse have been designed to examine the interac tions of aging and the ovary, and their mutual effects on neuroendocrine fu nction. In the pituitary, ovarian status and not age determines responsiven ess to gonadotropin hormone releasing hormone (GnRH), but estrogen (E-2) is an important mediator in CNS changes, and removal of the ovary (OVX) is de leterious to the neuroendocrine hypothalamus. OVX for just six days in youn g animals results in synaptic loss between noradrenergic terminals and gona dotropin hormone releasing hormone (GnRH) neurons. Long-term OVX, hypothesi zed to protect against neuroendocrine aging, fails to guard against any stu died age-related changes. Some age-related changes occur as early as midlif e. Although neuron number remains constant at middle age, opiatergic neuron s undergo significant functional changes by producing opiate antagonist pep tides. This change appears to be caused by alterations in the prohormone co nvertases, which cleave propeptide to peptide. Altered peptides may trigger the loss of reproductive capacity. The midlife shift in opiate peptide pro duction is a component of natural developmental processes that begin in the neonate and continue through old age. In the cholinergic system, E-2 media tes numbers of cholinergic receptors, cholinergic neurons, and cholinergic- modulated memory systems in both young and old animals. Regardless of age, ovarian steroids, if present at physiologic levels, are beneficial to the n euroendocrine CNS, and long-term deprivation from ovarian-produced factors is deleterious in the systems we have examined. Our studies have shown that deprivation from ovarian steroid hormones in the female appears to be a ma jor factor in the health of the CNS and in events associated with aging. (C ) 1998 Elsevier Science Inc.