Jon Levine, PhD
PhD, University of Illinois, Urbana
Director, Wisconsin National Primate Research Center
1220 Capitol Court
Madison, WI 53715-1299
The goal of my NICHD-funded research is to investigate the cellular and molecular mechanisms that mediate the physiological feedback actions of estrogens in the brain. For the past 30 years I have studied the neuroendocrine regulation of gonadotropin releasing hormone (GnRH) neurons, in part by developing and utilizing physiological methods to monitor and analyze GnRH neurosecretion in awake animals. My research has also focused on the mechanisms by which ovarian steroids exert their effects in the brain, the latter including the negative feedback mechanisms that maintain homeostatic control within the reproductive axis, as well as the positive feedback actions of steroids that culminate in release of preovulatory gonadotropin surges. My recent work has made use of newly developed mutant mice to analyze the cell signaling mechanisms that mediate negative and positive feedback actions of estradiol. These recent research findings have provided new evidence for distinct “classical” transcriptional pathways, as well as “non-classical” genotropic and non-genotropic pathways, that contribute very differently to the manifestation of estradiol’s different feedback effects and metabolic neuroendocrine actions.
Xu X, Zhao Z, Qin L, Wei W, Levine JE, Mirkin CA. (2008) Fluorescence recovery assay for the detection of protein-DNA binding. Analytical Chemistry. Jul 15;80(14):5616-21.
Acosta-Martínez M, Luo J, Elias C, Wolfe A, Levine JE. (2009) Male-biased effects of gonadotropin-releasing hormone neuron-specific deletion of the phosphoinositide 3-kinase regulatory subunit p85alpha on the reproductive axis. Endocrinology. Sep;150(9):4203-12.
Gottsch ML, Navarro VM, Zhao Z, Glidewell-Kenney C, Weiss J, Jameson JL, Clifton DK, Levine JE, Steiner RA. (2009) Regulation of Kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. Journal of Neuroscience. Jul 22;29(29):9390-5.
Singh SP, Wolfe A, Ng Y, DiVall SA, Buggs C, Levine JE, Wondisford FE, Radovick S. (2009) Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1). Biology of Reproduction. Sep;81(3):488-96.
Zhao Z, Park C, McDevitt MA, Glidewell-Kenney C, Chambon P, Weiss J, Jameson JL, Levine JE. (2009) p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis. Proceedings of the National Academy of Sciences. Apr 28;106(17):7221-6.
Abbott DH, Nicol LE, Levine JE, Xu N, Goodarzi MO, Dumesic DA. (2013) Nonhuman primate models of polycystic ovary syndrome. Molecular and Cellular Endocrinology. 5;373(1-2):21-8. doi: 10.1016/j.mce.2013.01.013.
Balthazart J, Levine JE. (2014) Endocrine disruptors: a relevant issue for neuroendocrinology also. Frontiers in Neuroendocrinology. 35(1):1. doi: 10.1016/j.yfrne.2013.09.002.
Dubois SL, Acosta-Martínez M, DeJoseph MR, Wolfe A, Radovick S, Boehm U, Urban JH, Levine JE. (2015) Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor α in kisspeptin neurons. Endocrinology. 156(3):1111-20. doi: 10.1210/en.2014-1851.
Bethea CL, Reddy AP, Flowers M, Shapiro RA, Colman RJ, Abbott DH, Levine JE. (2015) High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 3;58:71-80. doi: 10.1016/j.pnpbp.2014.11.008.