The pituitary glycoprotein hormones, including the gonadotropins LH and FSH, are dimeric glycoproteins which contain a common a subunit and different beta subunits. Characteristically the concentration of the alpha subunit usually exceeds the concentration of total glycoprotein hormone in pituitary or placental tissue. Thus, synthesis of the alpha and beta subunits may be independently regulated, and synthesis of the beta subunit may limit 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 pituitaries occurs during transcription, during a subsequent post-transcriptional processing event, or during translation. The cDNA clones will also be used to isolate their respective genes from a bovine genomic library. The overall structure of the gonadotropin genes will be determined as well as the nucleotide sequence of their coding regions. To further define the actual mechanisms which regulate gonadotropin gene expression, we will use mammalian expression vectors to: a) measure the activities of the alpha subunit and beta subunit promoters; b) determine whether there are hormonally responsive elements which flank the alpha subunit and beta subunit genes; and c) determine whether any of the gonadotropin genes contain """"""""enhancer""""""""-like sequences which affect the relative strength of their promoters. Successful completion of these objectives should offer new insights into the mechanisms which control expression of the gonadotropin genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK001316-04
Application #
3072349
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106