University of Nebraska Lincoln, 1990
Differentation, regulation and function of pituitary gonadotropes and placenta trophoblasts.
Mammalian reproduction is regulated by a number of hormones produced at various locations: hypothalamus in the brain, gonadotropes within the anterior pituitary gland, the gonads and also by the placenta during pregnancy. Luteinizing hormone (LH) and chorionic gonadotropin (CG) are synthesized in pituitary gonadotropes and placenta, respectively, and are essential to mammalian reproduction. Research in my laboratory is directed towards understanding the cellular and molecular mechanisms involved in regulating the genes encoding these hormones. One area of emphasis is on how gonadotropin-releasing hormone secreted by hypothalamic neurons signals to the pituitary to induce the expression of the genes for LH.
A second area focuses on elucidating the events associated with the differentiation of placental trophoblast cells and their acquisition of expression of CG. We use a variety of experimental approaches and models to examine cell differentiation and gonadotropin gene expression such as the study of DNA-protein and protein-protein interactions, DNA microarrays, promoter analysis, transgenic mice and human embryonic stem cells. Our overall goal is to identify the physiologically relevant molecular and cellular events responsible for regulating cell differentiation and expression of the gonadotropin subunit genes. This will provide a better understanding of how the reproductive system is normally regulated and ultimately, will provide clues as to how diseases, drugs and the environment impact reproductive success.
Wolfe, M.W. and Call, G.B. (1999) Early growth response protein 1 binds to the luteinizing hormone-ß promoter and mediates gonadotropin-releasing hormone-stimulated gene expression. Mol. Endocrinol. 13:752-763
Wolfe, M.W. (1999) The equine luteinizing hormone ß promoter contains two functional steroidogenic factor-1 response elements. Mol. Endocrinol. 13:1497-1510
Call, G.B. and Wolfe, M.W. (1999) Gonadotropin-releasing hormone activates the equine luteinizing hormone ß promoter through a protein kinase C/mitogen activated protein kinase pathway. Biol. Reprod. 61:715-23
Peters, T.J., B.M. Chapman, M.W. Wolfe, and M.J. Soares. (2000) Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways. J. Endocrinol. 165:443-56
Sharp, D.C., M.W. Wolfe, B.D. Cleaver and J. Nilson. (2001) Effects of estradiol-17ß administration on steady-state messenger ribonucleic acid (mRNA) encoding equine alpha and LH/CGß subunits in pituitaries of ovariectomized pony mares. Theriogenology. 55:1083-93
Thway, T.M., and M.W. Wolfe. (2001) Epidermal growth factor regulation of equine glycoprotein hormone alpha-subunit expression in trophoblast cells. Biol. Reprod. 65:197-203
Thway, T.M., C.M. Clay, J.K. Maher, D.K. Reed, K.J. McDowell, D.F. Antczak, R.L. Eckert, G.B. Call, J.H. Nilson and M.W. Wolfe. (2001) Immortalization of equine trophoblast cell lines of chorionic girdle cell lineage by simian virus-40 large T-antigen. J Endocrinol. 171:45-55
Zhang, T., M.W. Wolfe and M.S. Roberson. (2001) An early growth response protein (Egr) 1 cis element is required for gonadotropin-releasing hormone-induced mitogen-activated protein kinase phosphatase 2 gene expression. J. Biol. Chem. 276:45604-13
Call, G.B. and M.W. Wolfe. (2002) Species differences in GnRH activation of the LHß promoter: role of Egr1 and Sp1. Mol. Cell. Endocrinol. 189:85-96
Thway, T.M. and M.W. Wolfe. (2002) An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha-subunit expression in trophoblast cells. Biol. Reprod. 67:972-80
Soares, M.J. and M.W. Wolfe. (2004) Human embryonic stem cells assemble and fulfill their developmental destiny. Endocrinol. 145:1514-16.