Fos-induction in gonadotropin-releasing hormone neurons receiving vasoactive intestinal polypeptide innervation is reduced in middle-aged female rats

A hallmark of reproductive aging in rats is a delay in the initiation and p eak, and a decrease in the amplitude, of both proestrous and steroid-induce d surges of LH and a decrease in the number of GnRH neurons that express Fo s during the surge. The altered timing of the LH surge and the decline in F os expression in GnRH neurons may be due to changes in the rhythmic express ion of vasoactive intestinal polypeptide (VIP), a neuropeptide that carries time-of-day information from the circadian pacemaker, located in the supra chiasmatic nuclei (SCN), to GnRH neurons. The goals of our study were to de termine if aging alters 1) the innervation of GnRH neurons by VIP and 2) th e ability of VIP to activate GnRH neurons by examining the effects of aging on the number of GnRH neurons apposed by VIP fibers and the number of GnRH neurons that receive VIP input that express Fos. Immunocytochemistry for G nRH and VIP; or GnRH, VIP, and Fos was performed on tissue sections collect ed from young (2-4 mo), regularly cycling females and middle-aged (10-12 mo ) females in constant estrus. The number of GnRH neurons, GnRH neurons appo sed by VIP fibers, and GnRH neurons that express Fos and apposed by VIP fib ers were counted in both age groups. Our results clearly demonstrate that a ging does not alter the number of GnRH neurons that receive VIP innervation . However, the number of GnRH neurons that receive VIP innervation and coex press Fos decreases significantly. We conclude that the age-related delay i n the timing of the LH surge is not due to a change in VIP innervation of G nRH neurons, but instead may result from a decreased sensitivity of GnRH ne urons to VIP input.