University of Wisconsin–Madison

Jon E. Levine, PHD

Director, Wisconsin National Primate Research Center

Department

Jon E. LevineNeuroscience

Contact Information

Other web pages

Curriculum Vitae

Jon Levine’s Curriculm Vitae

Aligned research focus

Reproductive medicine, neuroscience, metabolism and obesity

Organ system/disease focus

Brain, infertility, obesity, metabolic syndrome

Research description

Our studies focus on the molecular, cellular and physiological actions of steroid hormones in the brain. Ovarian estrogens exert critically important actions in specific neuronal populations to regulate ovulatory cyclicity, reproductive behaviors, energy homeostasis and body weight. Estrogen receptor alpha (ERα) appears to mediate most of these effects, as disruption of ERα signaling leads to infertility and metabolic syndrome. ERα signaling mechanisms may include “classical genotropic” effects mediated by direct binding of receptor dimers to DNA, “non-classical genotropic” effects involving tethering of ERs to other transcription factors and “non-classical non-genotropic” actions mediated by cytoplasmic ERs coupled to membrane-initiated signal transduction pathways. Our studies are making use of conditional gene targeting to ascertain the cellular mechanisms by which ERα mediates E2 effects on these physiological and behavioral processes. We have utilized a novel mutant ERα knock-in mouse model, which confers non-classical genotropic and non-genotropic signaling in the absence of classical signaling, to determine that non-classical ERα signaling can convey E2 effects integral to homeostatic feedback control of reproductive hormone secretions, as well as E2 actions governing metabolic function and body weight regulation. We are currently developing viral vector-mediated gene knockdown approaches to probe these important signaling mechanisms in non-human primates.

Selected references

Kurian JR, Louis S, Keen KL, Wolfe A, Terasawa E, Levine JE. The
Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function. Endocrinology. 2016 Sep;157(9):3588-603.

Abbott DH, Levine JE, Dumesic DA. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys With PCOS-like Traits. Curr Pharm Des. 2016 Jul 15. [Epub ahead of print]

Cikla U, Chanana V, Kintner DB, Udho E, Eickhoff J, Sun W, Marquez S, Covert L, Otles A, Shapiro RA, Ferrazzano P, Vemuganti R, Levine JE, Cengiz P. ERα Signaling Is Required for TrkB-Mediated Hippocampal Neuroprotection in Female Neonatal Mice after Hypoxic Ischemic Encephalopathy(1,2,3). eNeuro. 2016 Jan 28;3(1).

Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE. Estradiol Restrains Prepubertal Gonadotropin Secretion in Female Mice via Activation of ERα in Kisspeptin Neurons. Endocrinology. 2016 Apr;157(4):1546-54.

Dubois SL, Acosta-Martínez M, DeJoseph MR, Wolfe A, Radovick S, Boehm U, Urban JH, Levine JE. Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor α in kisspeptin neurons. Endocrinology. 2015 Mar;156(3):1111-20.

Bethea CL, Reddy AP, Flowers M, Shapiro RA, Colman RJ, Abbott DH, Levine JE. High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Apr 3;58:71-80.

Abbott DH, Nicol LE, Levine JE, Xu N, Goodarzi MO, Dumesic DA. Nonhuman primate models of polycystic ovary syndrome. Mol Cell Endocrinol. 2013 Jul 5;373(1-2):21-8.