BIOLOGY OF REPRODUCTION 51, 1264-1272 (1994) A Reduced Proportion of Luteinizing Hormone (LH)-Releasing Hormone Neurons Express

Results of previous studies suggest that altered patterns of LHRH neurosecretion contribute to attenuated LH surges and the eventual cessation of ovulation in aging female rats. The present study compared evidence of LHRH neuronal activation in conjunction with the preovulatory and steroid-induced LH surge in young and middle-aged animals to determine whether age-related alterations could be detected. Double immunocytochemical protocols were used to colocalize LHRH and the protein product of the proto-oncogene c-fos, which increases within the nucleus of LHRH neurons in association with spontaneous or induced LH surges. The mean proportion of LHRH neurons containing immunoreactive Fos was higher in the brains of young compared to middle-aged females in association with both the preovulatory (p < 0.01) and the steroid-induced LH surge (p < 0.001). The time course of activation of LHRH neurons was delayed in the brains of aging females, and the proportion of double-labeled LHRH neurons remained elevated longer in the brains of young compared to middle-aged steroid-treated females. Moreover, regional differences in LHRH neuronal activation were observed both within and between age groups. The data presented suggest that reduced LHRH neuronal activation may contribute to the attenuation and eventual loss of preovulatory LH surges in middle-