Dynamic Changes in Gonadotropin Releasing Hormone Receptor mRNA Content in the Mediobasal Hypothalamus during the Rat Estrous Cycle

Abstract

The purpose of the present study was to determine if GnRH receptor mRNA levels in the rat brain undergo changes during the estrous cycle. We focused on the arcuate and ventromedial nuclei of the hypothalamus and on the hippocampus which are sites in the rat central nervous system that have been shown to contain measurable amounts of GnRH receptor mRNA. Groups of regularly cycling female rats were decapitated at 08.00 and 17.00 h of each day of the estrous cycle, trunk blood was collected for radioimmunoassay analysis of circulating LH levels, and the brains were processed for 'in situ' hybridization. A cDNA probe encoding the rat pituitary GnRH receptor was transcribed 'in vitro' in the presence of (33)P-alpha UTP and used under saturating conditions to label GnRH receptor mRNA. The results show that in the arcuate and ventromedial nuclei GnRH receptor mRNA levels are relatively high during diestrus 1, they decline slightly during diestrus 2 before they rise to the highest levels at 08.00 h of proestrus. By 17.00 h of proestrus, GnRH receptor mRNA levels had declined to the lowest levels of the estrous cycle where they remain through the morning of estrus. The GnRH receptor mRNA levels rise again sharply during the afternoon of estrus. The changes in the hippocampus follow a similar pattern in that a decline in GnRH receptor mRNA levels to its lowest levels occurs between 08.00 and 17.00 h of proestrus. However, the changes in the hippocampus did not reach statistical significance. It is concluded that GnRH receptor mRNA levels in the arcuate and ventromedial nuclei are upregulated in the morning of proestrus, probably by rising estradiol levels, in preparation for the GnRH-LH preovulatory surge while this effect of estradiol is not apparent in the hippocampus.