The long-term goal of this project is to find the cause and develop a treatment for human pituitary gonadotroph adenomas.
The specific aim for the next 4 years is to determine if absence of follistatin plays a role in the development of gonadotroph adenomas. The rationale for this aim is that these adenomas underexpress follistatin mRNA and peptide, and follistatin has been shown in a variety of tissues to inhibit the action of activin, which is to stimulate FSH secretion. The first approach will be to transfect gonadotroph adenoma cells with a sense follistatin cDNA to determine if increasing follistatin expression in those cells will decrease FSH secretion and cell division, and to transfect cultured nonadenomatous gonadotrophs with an antisense follistatin cDNA to determine if decreasing follistatin will increase FSH secretion and cell division. The second approach will be to construct transgenic mice whose gonadotroph cells, and only gonadotroph cells, underexpress follistatin. If the pituitaries of mice carrying the transgene do express the antisense transgene and underexpress sense follistatin mRNA and peptide, other F1 mice will be used to establish lines which will be observed for the development of gonadotroph adenomas.
