Evidence that endopeptidase-catalyzed luteinizing hormone releasing hormone cleavage contributes to the regulation of median eminence LHRH levels during positive steroid feedback.

In previous studies we provided evidence that the degradation of LHRH is regulated so as to contribute to the establishment of appropriate levels of the decapeptide during the events leading to gonadotropin secretion in the first estrous cycle at puberty in the rat. In the present report, we present the first evidence that this apparent regulation of LHRH degradation can be studied in an experimental positive feedback model. We show that LHRH degradation in the median eminence was decreased 3 h after progesterone administration, at a time when LHRH content in this region is increasing, and when serum levels of LH remained at basal levels. Six h after progesterone administration, at the time of the LH surge, median eminence LHRH degradation was still low and LHRH content had fallen to basal levels. Additionally, we exploited this model to examine the mechanism of peptidase activity change by showing that blockade of noradrenergic neurotransmission by diethyldithiocarbamate abolishes the inhibition of LHRH degradation observed prior to the secretion of LH. We conclude that the degradation of LHRH by an endopeptidase may contribute to the regulation of LHRH levels appropriate for gonadotropin release, and that this can be studied in the ovariectomized, estrogen-progesterone-treated rat.