The pituitary glycoprotein hormones, including the gonadotropins LH and FSH, are dimeric glycoproteins which contain a common Alpha subunit and different Beta subunits. A characteristic of these hormones is that the concentration of the Alpha subunit usually exceeds the concentration of total glycoprotein hormone in pituitary or placental tissue. This difference suggests that synthesis of the Alpha and Beta subunits is independently regulated, and that synthesis of the Beta subunit limits the assembly of the mature glycoprotein hormone. However, little is known about the molecular mechanisms which regulate the synthesis and accumulation of newly synthesized Alpha and Beta subunits. To address this question we will isolate and characterize cDNAs for each of the gonadotropin subunits from a bovine pituitary cDNA library. These cDNA probes will be used to determine whether regulation of gonadotropin synthesis in fetal or adult bovine pitutaries in vivo occurs during transcription, post-transcriptional processing, or translation. To further define the actual mechanisms which regulate gonadotropin gene expression we will use the cDNA clones to isolate gonadotropin genes from a bovine genomic library. We will determine the organization and nucleotide sequence of the these genes and scan their 5 feet and 3 feet flanking regions for highly conserved sequences. Successful completion of these objectives is essential to our long term goal of using site-directed mutagenesis and DNA-mediated gene transfer to determine whether 5 feet or 3 feet flanking sequences are required for hormonal regulation of gonadotropin gene expression. These studies will offer new insights into the mechanisms which control gonadotropin synthesis.
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