Changes in proopiomelanocortin messenger ribonucleic acid levels in the rostral periarcuate region of the female rat during the estrous cycle.

GnRH synthesis and release are regulated by a number of neurotransmitter systems. Several studies have implicated the opioidergic system as one of the important modulators of GnRH. To obtain an index of the activity of beta-endorphin-secreting neurons during the estrous cycle, we measured levels of proopiomelanocortin mRNA (POMC mRNA) in the periarcuate region at different cycle stages, using in situ hybridization. Ten female Sprague-Dawley rats (200-230 g) were killed at each of 11 times during the 4-day estrous cycle. Fresh frozen sections were made through the rostral arcuate nucleus and placed on gelatin-coated slides. A 48-base probe complementary to rat POMC mRNA was 3' end-labeled with [35S]dATP and applied to individual sections in hybridization buffer. Sections were washed and exposed to film. Relative amounts of POMC mRNA were measured by obtaining optical densities with an image analyzer. POMC mRNA levels varied significantly. At proestrus, they were low just before the onset of the LH surge, followed by a sharp rise that afternoon. On the day of estrus, POMC mRNA remained elevated and then declined again on metestrus. A second but smaller rise was seen in the late afternoon of metestrus. This pattern of changes in POMC mRNA is consistent with an inhibitory effect of beta-endorphin on GnRH after the midcycle surge and in the postovulatory phase of the cycle, while low levels of POMC mRNA in the early afternoon of proestrus may permit the release of GnRH, which triggers the LH surge. The changes in POMC mRNA approximately parallel changes in progesterone in the cycle.