The luteinizing hormone/choriogonadotropin receptor (LHR) plays a pivotal role in reproductive physiology. In the female, its expression in the ovary is necessary both for ovulation as well as for the initial maintenance of pregnancy. During follicular development, ovulation, luteinization, and luteolysis the levels of LHR vary greatly and are often under complex hormonal control. The cloning of the cDNA for the LHR has allowed our lab as well as other s to examine the levels of LHR mRNA which accompany known changes in LHR numbers in the ovary. t has been shown that there is in fact a very tight correlation between receptor numbers and mRNA levels, suggesting that regulation of transcriptional and/or post- transcriptional events related to the LHR gene are critical in the modulation of LHR receptor numbers. More recently, we have been able to demonstrate that the FSH(cAMP)-mediated increase in LHR mRNA in differentiating rat granulosa cells is mediated at least in part by an increase in the transcription of the LHR gene. Preliminary experiments also indicate that one or more regions within the 5'flanking region of the LHR gene mediate this stimulatory effect of cAMP. The experiments proposed herein are designed to further address the molecular mechanisms underlying the regulation of the LHR in the ovary, using the rat as a model system. Specifically, we propose to: 1. Determine the cis- and trans-acting factors which are involved in the ovarian expression of the LHR gene. 2. Determine whether FSH(cAMP)) stabilizes LHR mRNA in granulosa cells. 3. Determine the relative changes in LHR gene transcription and LHR mRNA are known to occur.
