DIFFERENTIAL-EFFECTS OF ESTROGEN AND PROGESTERONE ON LEVELS OF POMC MESSENGER-RNA LEVELS IN THE ARCUATE NUCLEUS - RELATIONSHIP TO THE TIMING OF LH SURGE RELEASE

Beta-endorphin is thought be an important inhibitor of LHRH neuronal a ctivity and also to play a role in conveying information about changes in steroid levels to LHRH neurons. We have previously shown that the mRNA encoding the precursor of beta-endorphin, proopiomelanocortin (PO MC), fluctuates during the estrous cycle with the most dramatic change s occurring on proestrus. POMC mRNA levels decline before the onset of LH surge release but then dramatically rise and remain elevated durin g the surge. In the present studies we tested the hypothesis that the decline in POMC mRNA levels immediately before the proestrous LH surge is mediated by estrogen and the rise during the surge by progesterone . To test this hypothesis, we compared changes in POMC mRNA levels bet ween ovariectomized (OVX) and OVX estrogen (E2)-treated rats and betwe en OVX E2-treated rats with and without progesterone. Animals were exa mined at hourly intervals after the administration of progesterone, th en at every 4 h during the LH surge. Using in situ hybridization histo chemistry, we found that E2 decreased POMC mRNA levels in OVX rats bef ore the onset of the LH surge and further suppressed levels during the surge. Compared to animals treated with E2 alone, progesterone advanc ed the time at which both the LH surge began and the time at which POM C mRNA levels declined. After a transient decline, POMC mRNA levels ro se in these progesterone-treated animals and remained elevated through out the period of the LH surge. These results support the hypothesis t hat progesterone times the LH surge and limits its appearance to one d ay by exerting a biphasic effect on the activity of beta-endorphinergi c neurons of the arcuate nucleus.