University of Nebraska Lincoln, 1990
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Regulation of the hypothalamic-pituitary-gonadal axis; Differentiation and function of 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. An area of interest is how gonadotropin-releasing hormone secreted by hypothalamic neurons signals to the pituitary to induce the expression of the genes for LH and also how gonadal steroids feedback to regulate the hypothalamus and pituitary.
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.
Roberson, M.S., S.P. Bliss, J. Xie, A. Navratil, T. Farmerie, M.W. Wolfe and C.M. Clay. 2005. Gonadotropin-releasing hormone induction of extracellular-signal regulated kinase is blocked by inhibition of calmodulin. Mol. Endocrinol. 19:2412-23.
Berghorn, K.A., P.A. Clark, B. Encarnacion, C.J. DeRegis, J. Folger, M.I. Morasso, M.J. Soares, M.W. Wolfe and M.S. Roberson. 2005. Developmental expression of the homeobox protein Distal-less 3 and its relationship to progesterone production in mouse placenta. J. Endocrinol 186:315-23.
Sahgal, N., L.N. Canham, T. Konno, M.W. Wolfe, and M.J. Soares. 2005. Modulation of trophoblast stem cell and giant cell phenotypes: analyses using the Rcho-1 cell model. Differentiation 73:452-62.
Jablonka-Shariff, A., J.F. Roser, G.R. Bousfield, M. W. Wolfe, L.E. Sibley, M. Colgin and I. Boime. 2007. Expression and bioactivity of a single chain recombinant equine luteinizing hormone (reLH). Theriogenology 67:311-20.
Chaturvedi, G., P.D. Simone, R. Ain, M.J. Soares, M.W. Wolfe. 2009. Noggin maintains pluripotency of human embryonic stem cells grown on Matrigel. Cell Proliferation 42:425-33.
McDonald, E.A. and M.W. Wolfe. 2009. Adiponectin attenuation of endocrine function within human term trophoblast cells. Endocrinology. 150:4358-65.
McDonald, E.A. and M.W. Wolfe. 2011. The pro-inflammatory role of adiponectin at the maternal-fetal interface. Amer. J. Reprod. Immunol. 66:128-36.
Dutta, D., S. Ray, P. Home, M. Larson, M.W. Wolfe and S. Paul. 2011. Self renewal vs. lineage commitment of embryonic stem cells: protein kinase C signaling shifts the balance. Stem Cells. 29:618-28.
Karim Rumi, M.A., P. Dhakal, K. Kubota, D. Chakraborty, T. Lei, M.A. Larson, M.W. Wolfe, K.F. Roby, J.L. Vivian and M.J. Soares. 2014. Generation of Esr1 knockout rats using zinc finger nuclease-mediated genome editing. Endocrinology. 155:1991-9.
Michael W. Wolfe, Ph.D.
3901 Rainbow Blvd.
Kansas City, KS 66160
F: (913) 588-7430