LOCALIZED CHANGES IN LHRH MESSENGER-RNA LEVELS AS CELLULAR CORRELATESOF THE POSITIVE FEEDBACK EFFECTS OF ESTROGEN ON LHRH NEURONS

The luteinizing hormone-releasing hormone (LHRH) system appears to be the final common pathway for integrating multiple estrogen-induced sig nals into a trigger for the preovulatory LH surge. Because LHRH neuron s do not contain estrogen receptors, we have had no cellular marker to identify LHRH neurons involved in triggering the LH surge. Using an e strogenized ovariectomized rat model, we selectively deprived brain re gions of estrogen action with microimplants of antiestrogen. We showed that the rostral medial preoptic area (MPOA) is required for estrogen -dependent LH surges and that LHRH neurons in this region are involved in the surge. Using in situ hybridization histochemistry, we compared temporal changes in LHRH mRNA levels in MPOA neurons in animals exhib iting LH surges with those in which LH surges were absent. We defined a characteristic pattern of changes in LHRH mRNA seen only in animals exhibiting the surge and, therefore, believe that these changes in LHR H mRNA levels are cellular correlates of the positive feedback effects of estrogen on LHRH neurons. These findings are exciting because we n ow have a cellular marker for detecting changes in the neuronal activi ty of subpopulations of the anatomically and functionally diverse LHRH system. We can use this marker in future studies to define the comple x neurocircuitry which mediates the effects of estrogen on LHRH neuron s. In addition, we are currently examining temporal changes in LHRH tr anscription rate, LHRH mRNA stability and LHRH translation to determin e the significance of changes in LHRH mRNA levels in terms of biosynth esis.