cFos Activity Identifies Recruitment of Luteinizing Hormone-Releasing Hormone Neurons During the Ascending Phase of the Proestrous Luteinizing Hormone Surge.

The proto-oncogene product of the c-fos gene, cFos, is a useful marker for luteinizing hormone-releasing hormone (LHRH) neuronal activation. While recent data indicate that in the rat, an LHRH surge plays an active role in stimulating the proestrous luteinizing hormone (LH) surge, the mechanics of the LHRH surge remain unknown. The aim of this study was to determine whether LHRH neuronal activation occurs entirely at the beginning of the LH surge or whether the number of LHRH neurons activated increases during the ascending phase of the surge. To accomplish this aim, we determined the relationship between the number of LHRH neurons expressing cFos and LH concentrations during the ascending limb of the proestrous LH surge. During the estrous cycle in the rat, on the afternoon of proestrus, the number of LHRH neurons expressing cFos increased as plasma LH levels increased to reach peak concentrations. The regression line describing these two variables had a very highly significant correlation coefficient, indicating a linear relationship. Treatment with RU486 to block progesterone's action on the afternoon of proestrus significantly reduced both the number of LHRH neurons expressing cFos and the magnitude of LH secretion during the entire ascending phase of the LH surge. An analysis of covariance with comparison of regression lines from untreated and RU486-treated animals revealed that while both sets of data established significant linear relationships between the degree of activation of LHRH neurons and plasma LH values, the slopes of the two lines were different (P = 0.031) with no statistical difference in the two intercepts. These data, together with the demonstration of an overall reduction of cFos intensity following removal of progesterone's actions, suggest progesterone alters the dynamics of LHRH neuronal activation by significantly reducing the recruitment of LHRH neurons and suppressing the level of activation of individual LHRH neurons. The results of our study support the hypothesis that the ascending phase of the LH surge results from the gradual recruitment of LHRH neurons into the active state.