We will examine the molecular mechanism through which androgens act at the level of the pituitary gonadotrope to regulate gonadotropin gene expression, using both in vitro and in vivo model systems.
Specific Aim l is to elucidate the mechanism(s) of androgen regulation of follicle-stimulating hormone beta (FSHbeta) and luteinizing hormone beta (LHbeta) gene expression in an immortalized gonadotrope cell line. In this Aim, we will address whether direct or indirect actions of androgen are utilized to regulate gonadotropin gene expression at the level of the gonadotrope, identify upstream elements of the FSHbeta3 and LHbeta genes that are required for androgen regulation, and examine the binding of androgen receptor to these defined regions of the FSHbeta and LHbeta genes.
Specific Aim 2 is to determine the role of androgen receptor in the regulation of FSHbeta and LHbeta gene expression within the pituitary gonadotrope in vivo using transgenic mice in which function of the androgen receptor has been blocked specifically within gonadotropes. The results of these studies will elucidate the molecular mechanisms through which androgens regulate gonadotropin gene expression at the level of the pituitary gonadotrope, thereby providing a more thorough understanding of the molecular mechanisms involved in steroid feedback regulation of reproduction.
| Spady, Thomas J; Shayya, Rana; Thackray, Varykina G et al. (2004) Androgen regulates follicle-stimulating hormone beta gene expression in an activin-dependent manner in immortalized gonadotropes. Mol Endocrinol 18:925-40 |
| Pernasetti, Flavia; Spady, Thomas J; Hall, Sara B et al. (2003) Pituitary tumorigenesis targeted by the ovine follicle-stimulating hormone beta-subunit gene regulatory region in transgenic mice. Mol Cell Endocrinol 203:169-83 |
